Spiro-condensed indoline derivatives as pesticides

ABSTRACT

The use of a compound of formula I 
     
       
         
         
             
             
         
       
     
     wherein Y is a single bond, C═O, C═S or S(O) m  where m is 0, 1 or 2;
 
R 1 , R 2 , R 3 , R 4 , R 8  and Ra are specified organic groups and p is 0, 1, 2, 3, 4, 5 or 6;
 
q is 0, 1, 2, 3, 4, 5 or 6; provided that when p is 2 then q is not 2;
 
p+q is 1, 2, 3, 4, 5 or 6; or salts or N-oxides thereof or compositions containing them and their using incontrolling insects, acarines, nematodes or molluscs. Novel compounds are also provided.

This application is a divisional of U.S. application Ser. No. 10/581,174filed May 31, 2006, which is a U.S. Nation Stage under 35 USC 371 ofInternational Application No. PCT/IB2004/004070 filed Dec. 9, 2004,which claims priority to GB 0328907.1 filed Dec. 12, 2003, the contentsof which are incorporated herein by reference.

The present invention relates to spiroindoline derivatives, to processesfor preparing them, to insecticidal, acaricidal, molluscicidal andnematicidal compositions comprising them and to methods of using them tocombat and control insect, acarine, mollusc and nematode pests.

Spiroindoline derivatives with pharmaceutical properties are disclosedin for example U.S. Pat. No. 5,763,471, WO9825605, WO9429309, WO9828297and WO9964002. Synthetic routes to selected compounds withpharmaceutical properties are described in Proc. Natl. Acad. Sci. USA(1995), 92, 7001, Tetrahedron (1997), 53, 10983 and Tetrahedron Letters(1997), 38, 1497. It has now surprisingly been found that certainspiroindolines have insecticidal properties.

The present invention therefore provides a method of combating andcontrolling insects, acarines, nematodes or molluscs which comprisesapplying to a pest, to a locus of a pest, or to a plant susceptible toattack by a pest an insecticidally, acaricidally, nematicidally ormolluscicidally effective amount of a compound of formula (I):

wherein Y is a single bond, C═O, C═S or S(O)_(m) where m is 0, 1 or 2;

R¹ is hydrogen, optionally substituted alkyl, optionally substitutedalkoxycarbonyl, optionally substituted alkylcarbonyl, aminocarbonyl,optionally substituted alkylaminocarbonyl, optionally substituteddialkylaminocarbonyl, optionally substituted aryl, optionallysubstituted heteroaryl, optionally substituted alkoxy, optionallysubstituted aryloxy, optionally substituted heteroaryloxy, optionallysubstituted heterocyclyloxy, cyano, optionally substituted alkenyl,optionally substituted alkynyl, optionally substituted cycloalkyl,optionally substituted cycloalkenyl, formyl, optionally substitutedheterocyclyl, optionally substituted alkylthio, NO or NR¹³R¹⁴ where R¹³and R¹⁴ are independently hydrogen, COR¹⁵, optionally substituted alkyl,optionally substituted aryl, optionally substituted heteroaryl,optionally substituted heterocyclyl or R¹³ and R¹⁴ together with the Natom to which they are attached form a group —N═C(R¹⁶)—NR¹⁷R¹⁸; R¹⁵ isH, optionally substituted alkyl, optionally substituted alkoxy,optionally substituted aryl, optionally substituted aryloxy optionallysubstituted heteroaryl, optionally substituted heteroaryloxy or NR¹⁹R²⁰;R¹⁶, R¹⁷ and R¹⁸ are each independently H or lower alkyl; R¹⁹ and R²⁰are independently optionally substituted alkyl, optionally substitutedaryl or optionally substituted heteroaryl;

R² and R³ are independently hydrogen, halogen, cyano, optionallysubstituted alkyl, optionally substituted alkoxy or optionallysubstituted aryl;

each R⁴ is independently halogen, nitro, cyano, optionally substitutedC₁₋₈ alkyl, optionally substituted C₂₋₆ alkenyl, optionally substitutedC₂₋₆ alkynyl, optionally substituted alkoxycarbonyl, optionallysubstituted alkylcarbonyl, optionally substituted alkylaminocarbonyl,optionally substituted dialkylaminocarbonyl, optionally substituted C₃₋₇cycloalkyl, optionally substituted aryl, optionally substitutedheteroaryl, optionally substituted heterocyclyl, optionally substitutedalkoxy, optionally substituted aryloxy, optionally substitutedheteroaryloxy, optionally substituted alkylthio or R²¹R²²N where R²¹ andR²² are, independently, hydrogen, C₁₋₈ alkyl, C₃₋₇ cycloalkyl, C₃₋₆alkenyl, C₃₋₆ alkynyl, C₃₋₇ cycloalkyl(C₁₋₄)alkyl, C₂₋₆ haloalkyl, C₁₋₆alkoxy(C₁₋₆)alkyl, C₁₋₆ alkoxycarbonyl or R²¹ and R²² together with theN atom to which they are attached form a five, six or seven-memberedheterocyclic ring which may contain one or two further heteroatomsselected from O, N or S and which may be optionally substituted by oneor two C₁₋₆ alkyl groups, or 2 adjacent groups R⁴ together with thecarbon atoms to which they are attached form a 4, 5, 6, or 7 memberedcarbocyclic or heterocyclic ring which may be optionally substituted byhalogen; n is 0, 1, 2, 3 or 4;

each Ra is independently hydrogen, halogen, hydroxy, cyano, optionallysubstituted C₁₋₈ alkyl, optionally substituted C₂₋₆ alkenyl, optionallysubstituted C₂₋₆ alkynyl, optionally substituted alkoxycarbonyl,optionally substituted alkylcarbonyl, optionally substitutedalkylaminocarbonyl, optionally substituted dialkylaminocarbonyl,optionally substituted C₃₋₇ cycloalkyl, optionally substituted aryl,optionally substituted heteroaryl, optionally substituted heterocyclyl,optionally substituted alkoxy, optionally substituted aryloxy,optionally substituted heteroaryloxy, optionally substituted alkylthio,optionally substituted arylthio or R²³R²⁴N where R²³ and R²⁴ are,independently, hydrogen, C₁₋₈ alkyl, C₃₋₇ cycloalkyl, C₃₋₆ alkenyl, C₃₋₆alkynyl, C₃₋₇ cycloalkyl(C₁₋₄)alkyl, C₂₋₆ haloalkyl, C₁₋₆alkoxy(C₁₋₆)alkyl, C₁₋₆ alkoxycarbonyl or R²³ and R²⁴ together with theN atom to which they are attached form a five, six or seven-memberedheterocyclic ring which may contain one or two further heteroatomsselected from O, N or S and which may be optionally substituted by oneor two C₁₋₆ alkyl groups, or two Ra groups attached to the same carbonatom are ═O or two Ra groups attached to adjacent carbon atoms form abond, or two Ra groups together with the carbon atom to which they areattached form a three- to seven-membered ring, that may be saturated orunsaturated, and that may contain one or two hetero atoms selected fromthe group consisting of N, O and S, and which may be optionallysubstituted by one or two C₁₋₆ alkyl groups; or two Ra groups togetherform a group —CH₂—, —CH═CH— or —CH₂CH₂; p is 0, 1, 2, 3, 4, 5 or 6; q is0, 1, 2, 3, 4, 5 or 6; provided that when p is 2 then q is not 2; p+q is1, 2, 3, 4, 5 or 6;

R⁸ is optionally substituted alkyl, optionally substituted alkenyl,optionally substituted alkynyl, optionally substituted cycloalkyl,optionally substituted aryl, optionally substituted alkoxy, optionallysubstituted aryloxy, optionally substituted alkoxycarbonyl, optionallysubstituted alkylcarbonyl or optionally substituted alkenylcarbonyl; orsalts or N-oxides thereof.

The compounds of formula (I) may exist in different geometric or opticalisomers or tautomeric forms. This invention covers all such isomers andtautomers and mixtures thereof in all proportions as well as isotopicforms such as deuterated compounds.

Each alkyl moiety either alone or as part of a larger group (such asalkoxy, alkoxycarbonyl, alkylcarbonyl, alkylaminocarbonyl,dialkylaminocarbonyl) is a straight or branched chain and is, forexample, methyl, ethyl, n-propyl, n-butyl, n-pentyl, n-hexyl,iso-propyl, n-butyl, sec-butyl, iso-butyl, tert-butyl or neo-pentyl. Thealkyl groups are suitably C₁ to C₁₂ alkyl groups, but are preferablyC₁-C₁₀, more preferably C₁-C₈, even more preferably preferably C₁-C₆ andmost preferably C₁-C₄ alkyl groups.

When present, the optional substituents on an alkyl moiety (alone or aspart of a larger group such as alkoxy, alkoxycarbonyl, alkylcarbonyl,alkylaminocarbonyl, dialkylaminocarbonyl) include one or more ofhalogen, nitro, cyano, NCS—, C₃₋₇ cycloalkyl (itself optionallysubstituted with C₁₋₆ alkyl or halogen), C₅₋₇ cycloalkenyl (itselfoptionally substituted with C₁₋₆ alkyl or halogen), hydroxy, C₁₋₁₀alkoxy, C₁₋₁₀ alkoxy(C₁₋₁₀)alkoxy, tri(C₁₋₄)alkylsilyl(C₁₋₆)alkoxy, C₁₋₆alkoxycarbonyl(C₁₋₁₀)alkoxy, C₁₋₁₀ haloalkoxy, aryl(C₁₋₄)-alkoxy (wherethe aryl group is optionally substituted), C₃₋₇ cycloalkyloxy (where thecycloalkyl group is optionally substituted with C₁₋₆ alkyl or halogen),C₂₋₁₀ alkenyloxy, C₂₋₁₀ alkynyloxy, SH, C₁₋₁₀ alkylthio, C₁₋₁₀haloalkylthio, aryl(C₁₋₄)alkylthio (where the aryl group is optionallysubstituted), C₃₋₇ cycloalkylthio (where the cycloalkyl group isoptionally substituted with C₁₋₆ alkyl or halogen),tri(C₁₋₄)alkylsilyl(C₁₋₆)alkylthio, arylthio (where the aryl group isoptionally substituted), C₁₋₆ alkylsulfonyl, C₁₋₆ haloalkylsulfonyl,C₁₋₆ alkylsulfinyl, C₁₋₆ haloalkylsulfinyl, arylsulfonyl (where the arylgroup may be optionally substituted), tri(C₁₋₄)alkylsilyl,aryldi(C₁₋₄)alkylsilyl, (C₁₋₄)alkyldiarylsilyl, triarylsilyl, C₁₋₁₀alkylcarbonyl, HO₂C, C₁₋₁₀ alkoxycarbonyl, aminocarbonyl, C₁₋₆alkylaminocarbonyl, di(C₁₋₆ alkyl)aminocarbonyl, N—(C₁₋₃ alkyl)-N—(C₁₋₃alkoxy)aminocarbonyl, C₁₋₆ alkylcarbonyloxy, arylcarbonyloxy (where thearyl group is optionally substituted), di(C₁₋₆)alkylaminocarbonyloxy,oximes such as ═NOalkyl, ═NOhaloalkyl and ═NOaryl (itself optionallysubstituted), aryl (itself optionally substituted), heteroaryl (itselfoptionally substituted), heterocyclyl (itself optionally substitutedwith C₁₋₆ alkyl or halogen), aryloxy (where the aryl group is optionallysubstituted), heteroaryloxy, (where the heteroaryl group is optionallysubstituted), heterocyclyloxy (where the heterocyclyl group isoptionally substituted with C₁₋₆ alkyl or halogen), amino, C₁₋₆alkylamino, di(C₁₋₆)alkylamino, C₁₋₆ alkylcarbonylamino,N—(C₁₋₆)alkylcarbonyl-N—(C₁₋₆)alkylamino, C₂₋₆ alkenylcarbonyl, C₂₋₆alkynylcarbonyl, C₃₋₆ alkenyloxycarbonyl, C₃₋₆ alkynyloxycarbonyl,aryloxycarbonyl (where the aryl group is optionally substituted) andarylcarbonyl (where the aryl group is optionally substituted).

Alkenyl and alkynyl moieties can be in the form of straight or branchedchains, and the alkenyl moieties, where appropriate, can be of eitherthe (E)- or (Z)-configuration. Examples are vinyl, allyl and propargyl.

When present, the optional substituents on alkenyl or alkynyl includethose optional substituents given above for an alkyl moiety.

In the context of this specification acyl is optionally substituted C₁₋₆alkylcarbonyl (for example acetyl), optionally substituted C₂₋₆alkenylcarbonyl, optionally substituted C₂₋₆ alkynylcarbonyl, optionallysubstituted arylcarbonyl (for example benzoyl) or optionally substitutedheteroarylcarbonyl.

Halogen is fluorine, chlorine, bromine or iodine.

Haloalkyl groups are alkyl groups which are substituted with one or moreof the same or different halogen atoms and are, for example, CF₃, CF₂Cl,CF₃CH₂ or CHF₂CH₂.

In the context of the present specification the terms “aryl” and“aromatic ring system” refer to ring systems which may be mono-, bi- ortricyclic. Examples of such rings include phenyl, naphthalenyl,anthracenyl, indenyl or phenanthrenyl. A preferred aryl group is phenyl.In addition, the terms “heteroaryl”, “heteroaromatic ring” or“heteroaromatic ring system” refer to an aromatic ring system containingat least one heteroatom and consisting either of a single ring or of twoor more fused rings. Preferably, single rings will contain up to threeand bicyclic systems up to four heteroatoms which will preferably bechosen from nitrogen, oxygen and sulphur. Examples of such groupsinclude furyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl,1,2,3-triazolyl, 1,2,4-triazolyl, oxazolyl, isoxazolyl, thiazolyl,isothiazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,3,4-oxadiazolyl,1,2,5-oxadiazolyl, 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl,1,3,4-thiadiazolyl, 1,2,5-thiadiazolyl, pyridyl, pyrimidinyl,pyridazinyl, pyrazinyl, 1,2,3-triazinyl, 1,2,4-triazinyl,1,3,5-triazinyl, benzofuryl, benzisofuryl, benzothienyl, benzisothienyl,indolyl, isoindolyl, indazolyl, benzothiazolyl, benzisothiazolyl,benzoxazolyl, benzisoxazolyl, benzimidazolyl, 2,1,3-benzoxadiazolequinolinyl, isoquinolinyl, cinnolinyl, phthalazinyl, quinazolinyl,quinoxalinyl, naphthyridinyl, benzotriazinyl, purinyl, pteridinyl andindolizinyl. Preferred examples of heteroaromatic radicals includepyridyl, pyrimidyl, triazinyl, thienyl, furyl, oxazolyl, isoxazolyl,2,1,3-benzoxadiazole and thiazolyl.

The terms heterocycle and heterocyclyl refer to a non-aromatic ringcontaining up to 10 atoms including one or more (preferably one or two)heteroatoms selected from O, S and N. Examples of such rings include1,3-dioxolane, tetrahydrofuran and morpholine.

When present, the optional substituents on heterocyclyl include C₁₋₆alkyl and C₁₋₆ haloalkyl as well as those optional substituents givenabove for an alkyl moiety.

Cycloalkyl includes cyclopropyl, cyclopentyl and cyclohexyl.

Cycloalkenyl includes cyclopentenyl and cyclohexenyl.

When present, the optional substituents on cycloalkyl or cycloalkenylinclude C₁₋₃ alkyl as well as those optional substituents given abovefor an alkyl moiety.

Carbocyclic rings include aryl, cycloalkyl and cycloalkenyl groups.

When present, the optional substituents on aryl or heteroaryl areselected independently, from halogen, nitro, cyano, NCS—, C₁₋₆ alkyl,C₁₋₆ haloalkyl, C₁₋₆ alkoxy-(C₁₋₆)alkyl, C₂₋₆ alkenyl, C₂₋₆ haloalkenyl,C₂₋₆ alkynyl, C₃₋₇ cycloalkyl (itself optionally substituted with C₁₋₆alkyl or halogen), C₅₋₇ cycloalkenyl (itself optionally substituted withC₁₋₆ alkyl or halogen), hydroxy, C₁₋₁₀ alkoxy, C₁₋₁₀alkoxy(C₁₋₁₀)alkoxy, tri(C₁₋₄)alkyl-silyl(C₁₋₆)alkoxy, C₁₋₆alkoxycarbonyl(C₁₋₁₀)alkoxy, C₁₋₁₀ haloalkoxy, aryl(C₁₋₄)alkoxy (wherethe aryl group is optionally substituted with halogen or C₁₋₆ alkyl),C₃₋₇ cycloalkyloxy (where the cycloalkyl group is optionally substitutedwith C₁₋₆ alkyl or halogen), C₂₋₁₀ alkenyloxy, C₂₋₁₀ alkynyloxy, SH,C₁₋₁₀ alkylthio, C₁₋₁₀ haloalkylthio, aryl(C₁₋₄)alkylthio C₃₋₇cycloalkylthio (where the cycloalkyl group is optionally substitutedwith C₁₋₆ alkyl or halogen), tri(C₁₋₄)-alkylsilyl(C₁₋₆)alkylthio,arylthio, C₁₋₆ alkylsulfonyl, C₁₋₆ haloalkylsulfonyl, C₁₋₆alkylsulfinyl, C₁₋₆ haloalkylsulfinyl, arylsulfonyl,tri(C₁₋₄)alkylsilyl, aryldi(C₁₋₄)-alkylsilyl, (C₁₋₄)alkyldiarylsilyl,triarylsilyl, C₁₋₁₀ alkylcarbonyl, HO₂C, C₁₋₁₀ alkoxycarbonyl,aminocarbonyl, C₁₋₆ alkylaminocarbonyl, di(C₁₋₆ alkyl)-aminocarbonyl,N—(C₁₋₃ alkyl)-N—(C₁₋₃ alkoxy)aminocarbonyl, C₁₋₆ alkylcarbonyloxy,arylcarbonyloxy, di(C₁₋₆)alkylamino-carbonyloxy, aryl (itself optionallysubstituted with C₁₋₆ alkyl or halogen), heteroaryl (itself optionallysubstituted with C₁₋₆ alkyl or halogen), heterocyclyl (itself optionallysubstituted with C₁₋₆ alkyl or halogen), aryloxy (where the aryl groupis optionally substituted with C₁₋₆ alkyl or halogen), heteroaryloxy(where the heteroaryl group is optionally substituted with C₁₋₆ alkyl orhalogen), heterocyclyloxy (where the heterocyclyl group is optionallysubstituted with C₁₋₆ alkyl or halogen), amino, C₁₋₆ alkylamino,di(C₁₋₆)alkylamino, C₁₋₆ alkylcarbonylamino,N—(C₁₋₆)alkylcarbonyl-N—(C₁₋₆)alkylamino, arylcarbonyl, (where the arylgroup is itself optionally substituted with halogen or C₁₋₆ alkyl) ortwo adjacent positions on an aryl or heteroaryl system may be cyclisedto form a 5, 6 or 7 membered carbocyclic or heterocyclic ring, itselfoptionally substituted with halogen or C₁₋₆ alkyl. Further substituentsfor aryl or heteroaryl include aryl carbonyl amino (where the aryl groupis substituted by C₁₋₆ alkyl or halogen), (C₁₋₆)alkyloxycarbonylamino(C₁₋₆)alkyloxycarbonyl-N—(C₁₋₆)alkylamino, aryloxycarbonylamino (wherethe aryl group is substituted by C₁₋₆ alkyl or halogen),aryloxycarbonyl-N—(C₁₋₆)alkylamino, (where the aryl group is substitutedby C₁₋₆ alkyl or halogen), arylsulphonylamino (where the aryl group issubstituted by C₁₋₆ alkyl or halogen), arylsulphonyl-N—(C₁₋₆)alkylamino(where the aryl group is substituted by C₁₋₆ alkyl or halogen),aryl-N—(C₁₋₆)alkylamino (where the aryl group is substituted by C₁₋₆alkyl or halogen), arylamino (where the aryl group is substituted byC₁₋₆ alkyl or halogen), heteroaryl amino (where the heteroaryl group issubstituted by C₁₋₆ alkyl or halogen), heterocyclylamino (where theheterocyclyl group is substituted by C₁₋₆ alkyl or halogen),aminocarbonylamino, C₁₋₆ alkylaminocarbonyl amino,di(C₁₋₆)alkylaminocarbonyl amino, arylaminocarbonyl amino where the arylgroup is substituted by C₁₋₆ alkyl or halogen),aryl-N—(C₁₋₆)alkylaminocarbonylamino where the aryl group is substitutedby C₁₋₆ alkyl or halogen), C₁₋₆ alkylaminocarbonyl-N—(C₁₋₆)alkyl amino,di(C₁₋₆)alkylaminocarbonyl-N—(C₁₋₆)alkyl amino,arylaminocarbonyl-N—(C₁₋₆)alkyl amino where the aryl group issubstituted by C₁₋₆ alkyl or halogen) andaryl-N—(C₁₋₆)alkylaminocarbonyl-N—(C₁₋₆)alkyl amino where the aryl groupis substituted by C₁₋₆ alkyl or halogen).

For substituted phenyl moieties, heterocyclyl and heteroaryl groups itis preferred that one or more substituents are independently selectedfrom halogen, C₁₋₆ alkyl, C₁₋₆ haloalkyl, C₁₋₆ alkoxy(C₁₋₆)alkyl, C₁₋₆alkoxy, C₁₋₆ haloalkoxy, C₁₋₆ alkylthio, C₁₋₆ haloalkylthio, C₁₋₆alkylsulfinyl, C₁₋₆ haloalkylsulfinyl, C₁₋₆ alkylsulfonyl, C₁₋₆haloalkylsulfonyl, C₂₋₆ alkenyl, C₂₋₆ haloalkenyl, C₂₋₆ alkynyl, C₃₋₇cycloalkyl, nitro, cyano, CO₂H, C₁₋₆ alkylcarbonyl, C₁₋₆ alkoxycarbonyl,R²⁵R²⁶N or R²⁷R²⁸NC(O); wherein R²⁵, R²⁶, R²⁷ and R²⁸ are,independently, hydrogen or C₁₋₆ alkyl. Further preferred substituentsare aryl and heteroaryl groups.

Haloalkenyl groups are alkenyl groups which are substituted with one ormore of the same or different halogen atoms.

It is to be understood that dialkylamino substituents include thosewhere the dialkyl groups together with the N atom to which they areattached form a five, six or seven-membered heterocyclic ring which maycontain one or two further heteroatoms selected from O, N or S and whichis optionally substituted by one or two independently selected(C₁₋₆)alkyl groups. When heterocyclic rings are formed by joining twogroups on an N atom, the resulting rings are suitably pyrrolidine,piperidine, thiomorpholine and morpholine each of which may besubstituted by one or two independently selected (C₁₋₆) alkyl groups.

Preferably the optional substituents on an alkyl moiety include one ormore of halogen, nitro, cyano, HO₂C, C₁₋₁₀ alkoxy (itself optionallysubstituted by C₁₋₁₀ alkoxy), aryl(C₁₋₄)alkoxy, C₁₋₁₀ alkylthio, C₁₋₁₀alkylcarbonyl, C₁₋₁₀ alkoxycarbonyl, C₁₋₆ alkylaminocarbonyl, di(C₁₋₆alkyl)aminocarbonyl, (C₁₋₆)alkylcarbonyloxy, optionally substitutedphenyl, heteroaryl, aryloxy, arylcarbonyloxy, heteroaryloxy,heterocyclyl, heterocyclyloxy, C₃₋₇ cycloalkyl (itself optionallysubstituted with (C₁₋₆)alkyl or halogen), C₃₋₇ cycloalkyloxy, C₅₋₇cycloalkenyl, C₁₋₆ alkylsulfonyl, C₁₋₆ alkylsulfinyl,tri(C₁₋₄)alkylsilyl, tri(C₁₋₄)alkylsilyl(C₁₋₆)alkoxy,aryldi(C₁₋₄)alkylsilyl, (C₁₋₄)alkyldiarylsilyl and triarylsilyl.

Preferably the optional substituents on alkenyl or alkynyl include oneor more of halogen, aryl and C₃₋₇ cycloalkyl.

A preferred optional substituent for heterocyclyl is C₁₋₆ alkyl.

Preferably the optional substituents for cycloalkyl include halogen,cyano and C₁₋₃ alkyl.

Preferably the optional substituents for cycloalkenyl include C₁₋₃alkyl, halogen and cyano.

Preferably Y is a single bond, C═O or S(O)_(m) where m is 0, 1 or 2.

More preferably Y is a single bond, C═O or SO₂.

Yet more preferably Y is a single bond or C═O.

Most preferably Y is C═O.

Preferably R¹ is hydrogen, C₁₋₆ alkyl, C₁₋₆ cyanoalkyl, C₁₋₆ haloalkyl,C₃₋₇ cycloalkyl(C₁₋₄)alkyl, C₁₋₆ alkoxy(C₁₋₆)alkyl,heteroaryl(C₁₋₆)alkyl (wherein the heteroaryl group may be optionallysubstituted by halo, nitro, cyano, C₁₋₆ alkyl, C₁₋₆ haloalkyl, C₁₋₆alkoxy, C₁₋₆ haloalkoxy, C₁₋₆ alkylsulfonyl, C₁₋₆ alkylsulfinyl, C₁₋₆alkylthio, C₁₋₆ alkoxycarbonyl, C₁₋₆ alkylcarbonylamino, arylcarbonyl,or two adjacent positions on the heteroaryl system may be cyclised toform a 5, 6 or 7 membered carbocyclic or heterocyclic ring, itselfoptionally substituted with halogen), aryl(C₁₋₆)alkyl (wherein the arylgroup may be optionally substituted by halo, nitro, cyano, C₁₋₆ alkyl,C₁₋₆ haloalkyl, C₁₋₆ alkoxy, C₁₋₆ haloalkoxy, C₁₋₆ alkylsulfonyl, C₁₋₆alkylsulfinyl, C₁₋₆ alkylthio, C₁₋₆ alkoxycarbonyl, C₁₋₆alkylcarbonylamino, arylcarbonyl, or two adjacent positions on the arylsystem may be cyclised to form a 5, 6 or 7 membered carbocyclic orheterocyclic ring, itself optionally substituted with halogen), C₁₋₆alkylcarbonylamino(C₁₋₆)alkyl, aryl (which may be optionally substitutedby halo, nitro, cyano, C₁₋₆ alkyl, C₁₋₆ haloalkyl, C₁₋₆ alkoxy, C₁₋₆haloalkoxy, C₁₋₆ alkylsulfonyl, C₁₋₆ alkylsulfinyl, C₁₋₆ alkylthio, C₁₋₆alkoxycarbonyl, C₁₋₆ alkylcarbonylamino, arylcarbonyl, or two adjacentpositions on the aryl system may be cyclised to form a 5, 6 or 7membered carbocyclic or heterocyclic ring, itself optionally substitutedwith halogen), heteroaryl (which may be optionally substituted by halo,nitro, cyano, C₁₋₆ alkyl, C₁₋₆ haloalkyl, C₁₋₆ alkoxy, C₁₋₆ haloalkoxy,C₁₋₆ alkylsulfonyl, C₁₋₆ alkylsulfinyl, C₁₋₆ alkylthio, C₁₋₆alkoxycarbonyl, C₁₋₆ alkylcarbonylamino, arylcarbonyl, or two adjacentpositions on the heteroaryl system may be cyclised to form a 5, 6 or 7membered carbocyclic or heterocyclic ring, itself optionally substitutedwith halogen), C₁₋₆ alkoxy, C₁₋₆ haloalkoxy, phenoxy (wherein the phenylgroup is optionally substituted by halogen, C₁₋₄ alkyl, C₁₋₄ alkoxy,C₁₋₄ haloalkyl, C₁₋₄ haloalkoxy, CN, NO₂, aryl, heteroaryl, amino ordialkylamino), heteroaryloxy (optionally substituted by halo, nitro,cyano, C₁₋₆ alkyl, C₁₋₆ haloalkyl, C₁₋₆ alkoxy or C₁₋₆ haloalkoxy),heterocyclyloxy (optionally substituted by halo, C₁₋₆ alkyl, C₁₋₆haloalkyl, C₁₋₆ alkoxy or C₁₋₆ haloalkoxy), cyano, C₂₋₆ alkenyl, C₂₋₆alkynyl, C₃₋₆ cycloalkyl, C₅₋₇ cycloalkenyl, heterocyclyl (optionallysubstituted by halo, nitro, cyano, C₁₋₆ alkyl, C₁₋₆ haloalkyl, C₁₋₆alkoxy or C₁₋₆ haloalkoxy), C₁₋₆ alkylthio, C₁₋₆ haloalkylthio orNR¹³R¹⁴ where R¹³ and R¹⁴ are independently hydrogen, C₁₋₆ alkyl, C₁₋₆haloalkyl, C₁₋₆ alkoxy(C₁₋₆)alkyl, phenyl (which may be optionallysubstituted by halogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ haloalkyl, C₁₋₄haloalkoxy, CN, NO₂, aryl, heteroaryl, amino, dialkylamino or C₁₋₄alkoxycarbonyl), phenyl (C₁₋₆)alkyl (wherein the phenyl group may beoptionally substituted by halogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄haloalkyl, C₁₋₄ haloalkoxy, CN, NO₂, aryl, heteroaryl, amino,dialkylamino, C₁₋₆ alkylsulfonyl, C₁₋₆ alkoxycarbonyl, or two adjacentpositions on the phenyl ring may be cyclised to form a 5, 6 or 7membered carbocyclic or heterocyclic ring, itself optionally substitutedwith halogen), heteroaryl (C₁₋₆)alkyl (wherein the heteroaryl group maybe optionally substituted by halo, nitro, cyano, C₁₋₆ alkyl, C₁₋₆haloalkyl, C₁₋₆ alkoxy, C₁₋₆ haloalkoxy, C₁₋₆ alkylsulfonyl, C₁₋₆alkylsulfinyl, C₁₋₆ alkylthio, C₁₋₆ alkoxycarbonyl, C₁₋₆alkylcarbonylamino, arylcarbonyl, or two adjacent positions on theheteroaryl system may be cyclised to form a 5, 6 or 7 memberedcarbocyclic or heterocyclic ring, itself optionally substituted withhalogen) or heteroaryl (which may be optionally substituted by halo,nitro, cyano, C₁₋₆ alkyl, C₁₋₆ haloalkyl, C₁₋₆ alkoxy or C₁₋₆haloalkoxy, C₁₋₄ alkoxycarbonyl C₁₋₆ alkylcarbonylamino,phenyloxycarbonylamino (wherein the phenyl group is optionallysubstituted by halogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ haloalkyl, C₁₋₄haloalkoxy, CN, NO₂, aryl, heteroaryl, amino or dialkylamino), amino,C₁₋₆ alkylamino or phenylamino (wherein the phenyl group is optionallysubstituted halogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ haloalkyl, C₁₋₄haloalkoxy, CN, NO₂, aryl, heteroaryl, amino or dialkylamino)).

More preferably R¹ is C₁₋₆ alkyl, C₁₋₆ haloalkyl, C₁₋₆alkoxy(C₁₋₆)alkyl, heteroaryl(C₁₋₃)alkyl (wherein the heteroaryl groupmay be optionally substituted by halo, nitro, cyano, C₁₋₆ alkyl, C₁₋₆haloalkyl, C₁₋₆ alkoxy, C₁₋₆ haloalkoxy, C₁₋₆ alkylsulfonyl, C₁₋₆alkoxycarbonyl, or two adjacent positions on the heteroaryl system maybe cyclised to form a 5, 6 or 7 membered carbocyclic or heterocyclicring, itself optionally substituted with halogen), phenyl(C₁₋₃)alkyl(wherein the phenyl group may be optionally substituted by halogen, C₁₋₄alkyl, C₁₋₄ alkoxy, C₁₋₄ haloalkyl, C₁₋₄ haloalkoxy, CN, NO₂, aryl,heteroaryl, amino, dialkylamino, C₁₋₆ alkylsulfonyl, C₁₋₆alkoxycarbonyl, or two adjacent positions on the phenyl ring may becyclised to form a 5, 6 or 7 membered carbocyclic or heterocyclic ring,itself optionally substituted with halogen), phenyl (which may beoptionally substituted by halogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄haloalkyl, C₁₋₄ haloalkoxy, CN, NO₂, aryl, heteroaryl, amino,dialkylamino, C₁₋₆ alkylsulfonyl, C₁₋₆ alkoxycarbonyl, or two adjacentpositions on the phenyl ring may be cyclised to form a 5, 6 or 7membered carbocyclic or heterocyclic ring, itself optionally substitutedwith halogen), heteroaryl (which may be optionally substituted by halo,nitro, cyano, C₁₋₆ alkyl, C₁₋₆ haloalkyl, C₁₋₆ alkoxy, C₁₋₆ haloalkoxy,C₁₋₆ alkylsulfonyl, C₁₋₆ alkoxycarbonyl, or two adjacent positions onthe heteroaryl system may be cyclised to form a 5, 6 or 7 memberedcarbocyclic or heterocyclic ring, itself optionally substituted withhalogen), C₁₋₆ alkoxy, C₁₋₆ haloalkoxy, C₂₋₆ alkenyl, heterocyclyl(optionally substituted by halo, cyano, C₁₋₆ alkyl, C₁₋₆ haloalkyl, C₁₋₆alkoxy or C₁₋₆ haloalkoxy), C₁₋₆ alkylthio, C₁₋₆ haloalkylthio orNR¹³R¹⁴ where R¹³ and R¹⁴ are independently hydrogen, C₁₋₆ alkyl or C₁₋₆haloalkyl, C₁₋₆ alkoxy(C₁₋₆)alkyl, C₂₋₆ alkylcarbonyl, phenylcarbonyl,(where the phenyl is optionally substituted by halogen, C₁₋₄ alkyl, C₁₋₄alkoxy, C₁₋₄ haloalkyl, C₁₋₄ haloalkoxy, CN, NO₂, aryl, heteroaryl,amino or dialkylamino), phenyl(C₁₋₃)alkyl (wherein the phenyl group maybe optionally substituted by halogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄haloalkyl, C₁₋₄ haloalkoxy, CN, NO₂, aryl, heteroaryl, amino,dialkylamino, C₁₋₆ alkylsulfonyl, C₁₋₆ alkoxycarbonyl, or two adjacentpositions on the phenyl ring may be cyclised to form a 5, 6 or 7membered carbocyclic or heterocyclic ring, itself optionally substitutedwith halogen) or heteroaryl(C₁₋₃)alkyl (wherein the heteroaryl group maybe optionally substituted by halo, nitro, cyano, C₁₋₆ alkyl, C₁₋₆haloalkyl, C₁₋₆ alkoxy, C₁₋₆ haloalkoxy, C₁₋₆ alkylsulfonyl, C₁₋₆alkylsulfinyl, C₁₋₆ alkylthio, C₁₋₆ alkoxycarbonyl, C₁₋₆alkylcarbonylamino, arylcarbonyl, or two adjacent positions on theheteroaryl system may be cyclised to form a 5, 6 or 7 memberedcarbocyclic or heterocyclic ring, itself optionally substituted withhalogen).

Even more preferably R¹ is C₁₋₆ alkyl, C₁₋₆ haloalkyl,heteroaryl(C₁₋₃)alkyl (wherein the heteroaryl group may be optionallysubstituted by halo, cyano, C₁₋₆ alkyl, C₁₋₆ haloalkyl and where theheteroaryl group is a thiazole, pyridine, pyrimidine, pyrazine orpyridazine ring), heteroaryl (optionally substituted by halo, cyano,C₁₋₆ alkyl, C₁₋₆ haloalkyl and where the heteroaryl group is a pyridine,pyrimidine, 2,1,3-benzoxadiazole, pyrazine or pyridazine ring), C₁₋₆alkoxy, C₁₋₆ alkoxy(C₁₋₆)alkyl, C₁₋₆ alkylamino, C₁₋₆alkoxy(C₁₋₆)alkylamino or heteroaryl(C₁₋₃)alkylamino (wherein theheteroaryl group may be optionally substituted by halo, cyano, C₁₋₆alkyl, C₁₋₆ haloalkyl and where the heteroaryl group is a thiazole,pyridine, pyrimidine, pyrazine or pyridazine ring).

Most preferably R¹ is pyridyl (optionally substituted by halo, C₁₋₃alkyl or C₁₋₃ haloalkyl) especially halo-substituted pyridyl.

It is preferred that R² and R³ are independently hydrogen, C₁₋₆ alkyl,C₁₋₆ haloalkyl, C₁₋₆ alkoxy or cyano.

More preferably R² and R³ are independently hydrogen, halogen, C₁₋₂alkyl, C₁₋₂ haloalkyl, C₁₋₂ alkoxy, cyano.

Even more preferably R² and R³ are independently hydrogen or C₁₋₄ alkyl.

Yet more preferably R² and R³ are independently hydrogen or methyl.

Most preferably R² and R³ are both hydrogen.

Preferably each R⁴ is independently halogen, cyano, C₁₋₈ alkyl, C₁₋₈haloalkyl, C₁₋₆ cyanoalkyl, C₁₋₆ alkoxy(C₁₋₆)alkyl, C₃₋₇cycloalkyl(C₁₋₆)alkyl, C₅₋₆ cycloalkenyl(C₁₋₆)alkyl, C₃₋₆alkenyloxy(C₁₋₆)alkyl, C₃₋₆ alkynyloxy(C₁₋₆)alkyl, aryloxy(C₁₋₆)alkyl,C₁₋₆ carboxyalkyl, C₁₋₆ alkylcarbonyl(C₁₋₆)alkyl, C₂₋₆alkenylcarbonyl(C₁₋₆)alkyl, C₂₋₆ alkynyl carbonyl(C₁₋₆)-alkyl, C₁₋₆alkoxycarbonyl(C₁₋₆)alkyl, C₃₋₆ alkenyloxycarbonyl(C₁₋₆)alkyl, C₃₋₆alkynyloxycarbonyl(C₁₋₆)alkyl, aryloxycarbonyl(C₁₋₆)alkyl, C₁₋₆alkylthio(C₁₋₆)alkyl, C₁₋₆ alkylsulfinyl(C₁₋₆)alkyl, C₁₋₆alkylsulfonyl(C₁₋₆)alkyl, aminocarbonyl(C₁₋₆)alkyl, C₁₋₆alkylaminocarbonyl(C₁₋₆)alkyl, di(C₁₋₆)alkylaminocarbonyl(C₁₋₆)alkyl,phenyl(C₁₋₄)alkyl (wherein the phenyl group is optionally substituted byhalogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ haloalkyl, C₁₋₄ haloalkoxy, CN,NO₂, aryl, heteroaryl, amino or dialkylamino), heteroaryl(C₁₋₄)alkyl(wherein the heteroaryl group is optionally substituted by halo, nitro,cyano, C₁₋₆ alkyl, C₁₋₆ haloalkyl, C₁₋₆ alkoxy or C₁₋₆ haloalkoxy),heterocyclyl(C₁₋₄)alkyl (wherein the heterocyclyl group is optionallysubstituted by halo, nitro, cyano, C₁₋₆ alkyl, C₁₋₆ haloalkyl, C₁₋₆alkoxy or C₁₋₆ haloalkoxy), C₂₋₆ alkenyl, aminocarbonyl(C₂₋₆)alkenyl,C₁₋₆ alkylaminocarbonyl(C₂₋₆)alkenyl,di(C₁₋₆)alkylaminocarbonyl(C₂₋₆)alkenyl, phenyl(C₂₋₄)-alkenyl, (whereinthe phenyl group is optionally substituted by halogen, C₁₋₄ alkyl, C₁₋₄alkoxy, C₁₋₄ haloalkyl, C₁₋₄ haloalkoxy, CN, NO₂, aryl, heteroaryl,amino or dialkylamino), C₂₋₆ alkynyl, trimethylsilyl(C₂₋₆)alkynyl,aminocarbonyl(C₂₋₆)alkynyl, C₁₋₆ alkylaminocarbonyl(C₂₋₆)alkynyl,di(C₁₋₆)alkylaminocarbonyl(C₂₋₆)alkynyl, C₁₋₆ alkoxycarbonyl, C₃₋₇cycloalkyl, C₃₋₇ halocycloalkyl, C₃₋₇ cyanocycloalkyl, C₁₋₃alkyl(C₃₋₇)-cycloalkyl, C₁₋₃ alkyl(C₃₋₇)halocycloalkyl,phenyl(optionally substituted by halogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄haloalkyl, C₁₋₄ haloalkoxy, CN, NO₂, aryl, heteroaryl, amino ordialkylamino), heteroaryl (optionally substituted by halo, nitro, cyano,C₁₋₆ alkyl, C₁₋₆ haloalkyl, C₁₋₆ alkoxy or C₁₋₆ haloalkoxy),heterocyclyl (wherein the heterocyclyl group is optionally substitutedby halo, nitro, cyano, C₁₋₆ alkyl, C₁₋₆ haloalkyl, C₁₋₆ alkoxy or C₁₋₆haloalkoxy), or 2 adjacent groups R⁴ together with the carbon atoms towhich they are attached form a 4, 5, 6 or 7 membered carbocylic orheterocyclic ring which may be optionally substituted by halogen, C₁₋₈alkoxy, C₁₋₆ haloalkoxy, phenoxy (optionally substituted by halo, nitro,cyano, C₁₋₆ alkyl, C₁₋₆ haloalkyl, C₁₋₆ alkoxy or C₁₋₆ haloalkoxy),heteroaryloxy (optionally substituted by halo, nitro, cyano, C₁₋₆ alkyl,C₁₋₆ haloalkyl, C₁₋₆ alkoxy or C₁₋₆ haloalkoxy), C₁₋₈ alkylthio orR¹⁹R²⁰N where R¹⁹ and R²⁰ are, independently, hydrogen, C₁₋₈ alkyl, C₃₋₇cycloalkyl, C₃₋₆ alkenyl, C₃₋₆ alkynyl, C₂₋₆ haloalkyl, C₁₋₆alkoxycarbonyl or R¹⁹ and R²⁰ together with the N atom to which they areattached form a five, six or seven-membered heterocyclic ring which maycontain one or two further heteroatoms selected from O, N or S and whichmay be optionally substituted by one or two C₁₋₆ alkyl groups; n is 0,1, 2 or 3.

More preferably each R⁴ is independently halogen, cyano, C₁₋₈ alkyl,C₁₋₈ haloalkyl, C₁₋₈ cyanoalkyl, C₁₋₆ alkoxy(C₁₋₆)alkyl, C₂₋₆ alkynyl,trimethylsilyl(C₂₋₆)alkynyl, C₁₋₆ alkoxycarbonyl, C₃₋₇ cycloalkyl, C₁₋₃alkyl (C₃₋₇) cycloalkyl, phenyl (optionally substituted by halogen, C₁₋₄alkyl, C₁₋₄ alkoxy, C₁₋₄ haloalkyl, C₁₋₄ haloalkoxy, CN, NO₂, aryl,heteroaryl, amino or dialkylamino), heterocyclyl (optionally substitutedby halo, nitro, cyano, C₁₋₆ alkyl, C₁₋₆ haloalkyl, C₁₋₆ alkoxy or C₁₋₆haloalkoxy), C₁₋₈ alkoxy, C₁₋₆ haloalkoxy, phenoxy (optionallysubstituted by halogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ haloalkyl, C₁₋₄haloalkoxy, CN, NO₂, aryl, heteroaryl, amino or dialkylamino),heteroaryloxy (optionally substituted by halo, nitro, cyano, C₁₋₃ alkyl,C₁₋₃ haloalkyl, C₁₋₃ alkoxy or C₁₋₃ haloalkoxy), di(C₁₋₈)alkylamino, or2 adjacent groups R⁴ together with the carbon atoms to which they areattached form a 4, 5, 6 or 7 membered carbocylic or heterocyclic ringwhich may be optionally substituted by halogen; n is 0, 1, 2 or 3.

Even more preferably each R⁴ is independently halogen, cyano, C₁₋₈alkyl, C₁₋₈ haloalkyl, C₁₋₈ cyanoalkyl, C₁₋₆ alkoxy(C₁₋₆)alkyl, C₂₋₆alkynyl, heterocyclyl (optionally substituted by C₁₋₆ alkyl), C₁₋₈alkoxy, C₁₋₆ haloalkoxy, phenoxy (optionally substituted by halo, cyano,C₁₋₃ alkyl or C₁₋₃ haloalkyl), heteroaryloxy (optionally substituted byhalo, cyano, C₁₋₃ alkyl or C₁₋₃ haloalkyl), di(C₁₋₈)alkylamino or 2adjacent groups R⁴ together with the carbon atoms to which they areattached form a 4, 5, 6 or 7 membered carbocylic or heterocyclic ringwhich may be optionally substituted by halogen; n is 0, 1, 2 or 3.

Yet more preferably each R⁴ is independently fluoro, chloro, bromo,cyano, C₁₋₄ alkyl, C₁₋₄ haloalkyl, C₁₋₄ cyanoalkyl or C₁₋₃alkoxy(C₁₋₃)alkyl; n is 0, 1 or 2.

Most preferably each R⁴ is independently fluoro, chloro, bromo, C₁₋₄alkyl or C₁₋₄ haloalkyl; n is 1 or 2.

Preferably R⁸ is C₁₋₁₀ alkyl, C₁₋₁₀ haloalkyl, aryl(C₁₋₆)alkyl (whereinthe aryl group is optionally substituted by halogen, C₁₋₄ alkyl, C₁₋₄alkoxy, C₁₋₄ haloalkyl, C₁₋₄ haloalkoxy, CN, NO₂, aryl, heteroaryl,amino or dialkylamino), heteroaryl(C₁₋₆)alkyl (wherein the heteroarylgroup is optionally substituted by halogen, C₁₋₄ alkyl, C₁₋₄ alkoxy,C₁₋₄ haloalkyl, C₁₋₄ haloalkoxy, CN, NO₂, aryl, heteroaryl, amino ordialkylamino), arylcarbonyl-(C₁₋₆)alkyl (wherein the aryl group may beoptionally substituted by halogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄haloalkyl, C₁₋₄ haloalkoxy, CN, NO₂, aryl, heteroaryl, amino ordialkylamino and the alkyl group may be optionally substituted by aryl),C₂₋₈ alkenyl, C₂₋₈ haloalkenyl, aryl(C₂₋₆)-alkenyl (wherein the arylgroup is optionally substituted halogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄haloalkyl, C₁₋₄ haloalkoxy, CN, NO₂, aryl, heteroaryl, amino ordialkylamino, C₁₋₆ alkoxycarbonyl, or two adjacent substituents cancyclise to form a 5, 6 or 7 membered carbocyclic or heterocyclic ring),heteroaryl(C₂₋₆)-alkenyl (wherein the heteroaryl group is optionallysubstituted halogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ haloalkyl, C₁₋₄haloalkoxy, CN, NO₂, aryl, heteroaryl, amino or dialkylamino, C₁₋₆alkoxycarbonyl, or two adjacent substituents can cyclise to form a 5, 6or 7 membered carbocyclic or heterocyclic ring), C₂₋₆ alkynyl,phenyl(C₂₋₆)alkynyl (wherein the phenyl group is optionally substitutedby halogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ haloalkyl, C₁₋₄ haloalkoxy,CN, NO₂, aryl, heteroaryl, amino or dialkylamino), C₃₋₇ cycloalkyl, C₁₋₆alkoxycarbonyl, C₁₋₆ alkylcarbonyl, C₁₋₆ haloalkylcarbonyl oraryl(C₂₋₆)alkenylcarbonyl (wherein the aryl group may be optionallysubstituted halogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ haloalkyl, C₁₋₄haloalkoxy, CN, NO₂, aryl, heteroaryl, amino or dialkylamino), or—C(R⁵¹)(R⁵²)—[CR⁵³═CR⁵⁴]z-R⁵⁵ where z is 1 or 2, R⁵¹ and R⁵² are eachindependently H, halo or C₁₋₂ alkyl, R⁵³ and R⁵⁴ are each independentlyH, halogen, C₁₋₄ alkyl or C₁₋₄ haloalkyl and R⁵⁵ is optionallysubstituted aryl or optionally substituted heteroaryl.

More preferably R⁸ is phenyl(C₁₋₄)alkyl (wherein the phenyl group isoptionally substituted by halogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄haloalkyl, C₁₋₄ haloalkoxy, CN, NO₂, aryl, heteroaryl, amino ordialkylamino), heteroaryl(C₁₋₆)alkyl (wherein the heteroaryl group isoptionally substituted halogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ haloalkyl,C₁₋₄ haloalkoxy, CN, NO₂, aryl, heteroaryl, amino or dialkylamino),phenyl(C₂₋₆)alkenyl (wherein the phenyl group is optionally substitutedby halogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ haloalkyl, C₁₋₄ haloalkoxy,CN, NO₂, aryl, heteroaryl, amino or dialkylamino),heteroaryl(C₂₋₆)alkenyl (wherein the heteroaryl group is optionallysubstituted by halogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ haloalkyl, C₁₋₄haloalkoxy, CN, NO₂, aryl, heteroaryl, amino or dialkylamino) orphenyl(C₂₋₆)alkynyl (wherein the phenyl group is optionally substitutedby halogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ haloalkyl, C₁₋₄ haloalkoxy,CN, NO₂, aryl, heteroaryl, amino or dialkylamino, or—C(R⁵¹)(R⁵²)—[CR⁵³═CR⁵⁴]_(z)—R⁵⁵ where z is 1 or 2, R⁵¹ and R⁵² are eachindependently H, halo or C₁₋₂ alkyl, R⁵³ and R⁵⁴ are each independentlyH, halogen, C₁₋₄ alkyl or C₁₋₄ haloalkyl and R⁵⁵ is optionallysubstituted aryl or optionally substituted heteroaryl.

Most preferably R⁸ is —C(R⁵¹)(R⁵²)—[CR⁵³═CR⁵⁴]_(z)—R⁵⁵ where z is 1 or2, preferably 1, R⁵¹ and R⁵² are each independently H, halo or C₁₋₂alkyl, R⁵³ and R⁵⁴ are each independently H, halogen, C₁₋₄ alkyl or C₁₋₄haloalkyl and R⁵⁵ is phenyl substituted by halogen, C₁₋₄ alkyl, C₁₋₄alkoxy, C₁₋₄ haloalkyl, C₁₋₄ haloalkoxy, CN, NO₂, aryl, heteroaryl,amino or dialkylamino or heteroaryl substituted by halogen, C₁₋₄ alkyl,C₁₋₄ alkoxy, C₁₋₄ haloalkyl, C₁₋₄ haloalkoxy, CN, NO₂, aryl, heteroaryl,amino or dialkylamino.

R⁵¹ and R⁵² are preferably hydrogen.

R⁵³ and R⁵⁴ are preferably hydrogen or halogen, especially hydrogen. R⁵⁵is preferably phenyl substituted with one to three substituents selectedfrom halogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ haloalkyl, C₁₋₄ haloalkoxy,CN, NO₂, aryl, heteroaryl, amino or dialkylamino.

Preferably each Ra is independently hydrogen, halo, cyano, C₁₋₃ alkyl,hydroxy or two Ra groups together with the carbon atom to which they areattached form a carbonyl group

More preferably each Ra is independently hydrogen, fluoro, methyl,hydroxy or two Ra groups together with the carbon atom to which they areattached form a carbonyl group

Most preferably each Ra is hydrogen.

Preferably p is 1 or 2 and q is 2 or 3 and p+q is 3, 4 or 5.

More preferably p is 1 or 2 and q is 2 or 3.

Most preferably p is 1 and q is 2 or 3.

One group of preferred compounds of formula (I) are those where Y isC(O) and R¹ is NR¹³R¹⁴ where R¹³ and R¹⁴ are as defined above

Certain compounds of formula (I) are novel and as such form a furtheraspect of the invention. One group of novel compounds are compounds offormula I′

wherein Y is CO, R² and R³ are both hydrogen and R¹, R⁴, R⁸, R^(a), n, pand q are as defined in relation to formula I provided that when n is 0,p is 1, q is 2, R1 is CH₃ and all groups Ra are H then R⁸ is not H,methyl, benzyl or CH₂—CH═CH₂ and when n is 0, (CRa₂)_(p) is CH-phenyl,(CRa₂)q is (CH₂)₂ and R¹ is methyl then R⁸ is not COOCH₃.

The compounds in Tables I to CCIV below illustrate the compounds of theinvention.

Table I provides 782 compounds of formula Ia

wherein each Ra is H, p is 1, q is 2 and the values of R⁸, R^(4a),R^(4b), R^(4c) and R^(4d) are given in Table 1

TABLE 1 Compound No R⁸ R^(4a) R^(4b) R^(4c) R^(4d) I-1 4-chlorobenzyl HH H H I-2 Cinnamyl H H H H I-3 4-chlorocinnamyl H H H H I-44-fluorocinnamyl H H H H I-5 4-bromocinnamyl H H H H I-64-trifluoromethylcinnamyl H H H H I-7 4-trifluoromethoxycinnamyl H H H HI-8 4-pentafluoroethoxycinnamyl H H H H I-9 4-methoxycinnamyl H H H HI-10 4-ethoxycinnamyl H H H H I-11 4-cyanocinnamyl H H H H I-123-(6-chloro-pyridin-3-yl)-allyl H H H H I-133-(4-chlorophenyl)-but-2-enyl H H H H I-143-(4-chlorophenyl)-3-fluoro-allyl H H H H I-153-chloro-4-fluoro-cinnamyl H H H H I-16 3,5-dichloro-cinnamyl H H H HI-17 5-phenyl-penta-2,4-dienyl H H H H I-184-isopropyloxycarbonylamino-cinnamyl H H H H I-193-naphthalen-2-yl-allyl H H H H I-203-(5-trifluoromethyl-pyridin-2-yl)-allyl H H H H I-213-(5-chloro-pyridin-2-yl)-allyl H H H H I-22 3-pyridin-4-yl-allyl H H HH I-23 3-(2-Chloro-pyridin-4-yl)-allyl H H H H I-24 4-chlorobenzyl H F HH I-25 Cinnamyl H F H H I-26 4-chlorocinnamyl H F H H I-274-fluorocinnamyl H F H H I-28 4-bromocinnamyl H F H H I-294-trifluoromethylcinnamyl H F H H I-30 4-trifluoromethoxycinnamyl H F HH I-31 4-pentafluoroethoxycinnamyl H F H H I-32 4-methoxycinnamyl H F HH I-33 4-ethoxycinnamyl H F H H I-34 4-cyanocinnamyl H F H H I-353-(6-chloro-pyridin-3-yl)-allyl H F H H I-363-(4-chlorophenyl)-but-2-enyl H F H H I-373-(4-chlorophenyl)-3-fluoro-allyl H F H H I-383-chloro-4-fluoro-cinnamyl H F H H I-39 3,5-dichloro-cinnamyl H F H HI-40 5-phenyl-penta-2,4-dienyl H F H H I-414-isopropyloxycarbonylamino-cinnamyl H F H H I-423-naphthalen-2-yl-allyl H F H H I-433-(5-trifluoromethyl-pyridin-2-yl)-allyl H F H H I-443-(5-chloro-pyridin-2-yl)-allyl H F H H I-45 3-pyridin-4-yl-allyl H F HH I-46 3-(2-Chloro-pyridin-4-yl)-allyl H F H H I-47 4-chlorobenzyl H ClH H I-48 Cinnamyl H Cl H H I-49 4-chlorocinnamyl H Cl H H I-504-fluorocinnamyl H Cl H H I-51 4-bromocinnamyl H Cl H H I-524-trifluoromethylcinnamyl H Cl H H I-53 4-trifluoromethoxycinnamyl H ClH H I-54 4-pentafluoroethoxycinnamyl H Cl H H I-55 4-methoxycinnamyl HCl H H I-56 4-ethoxycinnamyl H Cl H H I-57 4-cyanocinnamyl H Cl H H I-583-(6-chloro-pyridin-3-yl)-allyl H Cl H H I-593-(4-chlorophenyl)-but-2-enyl H Cl H H I-603-(4-chlorophenyl)-3-fluoro-allyl H Cl H H I-613-chloro-4-fluoro-cinnamyl H Cl H H I-62 3,5-dichloro-cinnamyl H Cl H HI-63 5-phenyl-penta-2,4-dienyl H Cl H H I-644-isopropyloxycarbonylamino-cinnamyl H Cl H H I-653-naphthalen-2-yl-allyl H Cl H H I-663-(5-trifluoromethyl-pyridin-2-yl)-allyl H Cl H H I-673-(5-chloro-pyridin-2-yl)-allyl H Cl H H I-68 3-pyridin-4-yl-allyl H ClH H I-69 3-(2-Chloro-pyridin-4-yl)-allyl H Cl H H I-70 4-chlorobenzyl HBr H H I-71 Cinnamyl H Br H H I-72 4-chlorocinnamyl H Br H H I-734-fluorocinnamyl H Br H H I-74 4-bromocinnamyl H Br H H I-754-trifluoromethylcinnamyl H Br H H I-76 4-trifluoromethoxycinnamyl H BrH H I-77 4-pentafluoroethoxycinnamyl H Br H H I-78 4-methoxycinnamyl HBr H H I-79 4-ethoxycinnamyl H Br H H I-80 4-cyanocinnamyl H Br H H I-813-(6-chloro-pyridin-3-yl)-allyl H Br H H I-823-(4-chlorophenyl)-but-2-enyl H Br H H I-833-(4-chlorophenyl)-3-fluoro-allyl H Br H H I-843-chloro-4-fluoro-cinnamyl H Br H H I-85 3,5-dichloro-cinnamyl H Br H HI-86 5-phenyl-penta-2,4-dienyl H Br H H I-874-isopropyloxycarbonylamino-cinnamyl H Br H H I-883-naphthalen-2-yl-allyl H Br H H I-893-(5-trifluoromethyl-pyridin-2-yl)-allyl H Br H H I-903-(5-chloro-pyridin-2-yl)-allyl H Br H H I-91 3-pyridin-4-yl-allyl H BrH H I-92 3-(2-Chloro-pyridin-4-yl)-allyl H Br H H I-93 4-chlorobenzyl HCN H H I-94 Cinnamyl H CN H H I-95 4-chlorocinnamyl H CN H H I-964-fluorocinnamyl H CN H H I-97 4-bromocinnamyl H CN H H I-984-trifluoromethylcinnamyl H CN H H I-99 4-trifluoromethoxycinnamyl H CNH H I-100 4-pentafluoroethoxycinnamyl H CN H H I-101 4-methoxycinnamyl HCN H H I-102 4-ethoxycinnamyl H CN H H I-103 4-cyanocinnamyl H CN H HI-104 3-(6-chloro-pyridin-3-yl)-allyl H CN H H I-1053-(4-chlorophenyl)-but-2-enyl H CN H H I-1063-(4-chlorophenyl)-3-fluoro-allyl H CN H H I-1073-chloro-4-fluoro-cinnamyl H CN H H I-108 3,5-dichloro-cinnamyl H CN H HI-109 5-phenyl-penta-2,4-dienyl H CN H H I-1104-isopropyloxycarbonylamino-cinnamyl H CN H H I-1113-naphthalen-2-yl-allyl H CN H H I-1123-(5-trifluoromethyl-pyridin-2-yl)-allyl H CN H H I-1133-(5-chloro-pyridin-2-yl)-allyl H CN H H I-114 3-pyridin-4-yl-allyl H CNH H I-115 3-(2-Chloro-pyridin-4-yl)-allyl H CN H H I-116 4-chlorobenzylH OMe H H I-117 Cinnamyl H OMe H H I-118 4-chlorocinnamyl H OMe H HI-119 4-fluorocinnamyl H OMe H H I-120 4-bromocinnamyl H OMe H H I-1214-trifluoromethylcinnamyl H OMe H H I-122 4-trifluoromethoxycinnamyl HOMe H H I-123 4-pentafluoroethoxycinnamyl H OMe H H I-1244-methoxycinnamyl H OMe H H I-125 4-ethoxycinnamyl H OMe H H I-1264-cyanocinnamyl H OMe H H I-127 3-(6-chloro-pyridin-3-yl)-allyl H OMe HH I-128 3-(4-chlorophenyl)-but-2-enyl H OMe H H I-1293-(4-chlorophenyl)-3-fluoro-allyl H OMe H H I-1303-chloro-4-fluoro-cinnamyl H OMe H H I-131 3,5-dichloro-cinnamyl H OMe HH I-132 5-phenyl-penta-2,4-dienyl H OMe H H I-1334-isopropyloxycarbonylamino-cinnamyl H OMe H H I-1343-naphthalen-2-yl-allyl H OMe H H I-1353-(5-trifluoromethyl-pyridin-2-yl)-allyl H OMe H H I-1363-(5-chloro-pyridin-2-yl)-allyl H OMe H H I-137 3-pyridin-4-yl-allyl HOMe H H I-138 3-(2-Chloro-pyridin-4-yl)-allyl H OMe H H I-1394-chlorobenzyl H OCF₃ H H I-140 Cinnamyl H OCF₃ H H I-1414-chlorocinnamyl H OCF₃ H H I-142 4-fluorocinnamyl H OCF₃ H H I-1434-bromocinnamyl H OCF₃ H H I-144 4-trifluoromethylcinnamyl H OCF₃ H HI-145 4-trifluoromethoxycinnamyl H OCF₃ H H I-1464-pentafluoroethoxycinnamyl H OCF₃ H H I-147 4-methoxycinnamyl H OCF₃ HH I-148 4-ethoxycinnamyl H OCF₃ H H I-149 4-cyanocinnamyl H OCF₃ H HI-150 3-(6-chloro-pyridin-3-yl)-allyl H OCF₃ H H I-1513-(4-chlorophenyl)-but-2-enyl H OCF₃ H H I-1523-(4-chlorophenyl)-3-fluoro-allyl H OCF₃ H H I-1533-chloro-4-fluoro-cinnamyl H OCF₃ H H I-154 3,5-dichloro-cinnamyl H OCF₃H H I-155 5-phenyl-penta-2,4-dienyl H OCF₃ H H I-1564-isopropyloxycarbonylamino-cinnamyl H OCF₃ H H I-1573-naphthalen-2-yl-allyl H OCF₃ H H I-1583-(5-trifluoromethyl-pyridin-2-yl)-allyl H OCF₃ H H I-1593-(5-chloro-pyridin-2-yl)-allyl H OCF₃ H H I-160 3-pyridin-4-yl-allyl HOCF₃ H H I-161 3-(2-Chloro-pyridin-4-yl)-allyl H OCF₃ H H I-1624-chlorobenzyl H CH₃ H H I-163 Cinnamyl H CH₃ H H I-164 4-chlorocinnamylH CH₃ H H I-165 4-fluorocinnamyl H CH₃ H H I-166 4-bromocinnamyl H CH₃ HH I-167 4-trifluoromethylcinnamyl H CH₃ H H I-1684-trifluoromethoxycinnamyl H CH₃ H H I-169 4-pentafluoroethoxycinnamyl HCH₃ H H I-170 4-methoxycinnamyl H CH₃ H H I-171 4-ethoxycinnamyl H CH₃ HH I-172 4-cyanocinnamyl H CH₃ H H I-173 3-(6-chloro-pyridin-3-yl)-allylH CH₃ H H I-174 3-(4-chlorophenyl)-but-2-enyl H CH₃ H H I-1753-(4-chlorophenyl)-3-fluoro-allyl H CH₃ H H I-1763-chloro-4-fluoro-cinnamyl H CH₃ H H I-177 3,5-dichloro-cinnamyl H CH₃ HH I-178 5-phenyl-penta-2,4-dienyl H CH₃ H H I-1794-isopropyloxycarbonylamino-cinnamyl H CH₃ H H I-1803-naphthalen-2-yl-allyl H CH₃ H H I-1813-(5-trifluoromethyl-pyridin-2-yl)-allyl H CH₃ H H I-1823-(5-chloro-pyridin-2-yl)-allyl H CH₃ H H I-183 3-pyridin-4-yl-allyl HCH₃ H H I-184 3-(2-Chloro-pyridin-4-yl)-allyl H CH₃ H H I-1854-chlorobenzyl H CF₃ H H I-186 Cinnamyl H CF₃ H H I-187 4-chlorocinnamylH CF₃ H H I-188 4-fluorocinnamyl H CF₃ H H I-189 4-bromocinnamyl H CF₃ HH I-190 4-trifluoromethylcinnamyl H CF₃ H H I-1914-trifluoromethoxycinnamyl H CF₃ H H I-192 4-pentafluoroethoxycinnamyl HCF₃ H H I-193 4-methoxycinnamyl H CF₃ H H I-194 4-ethoxycinnamyl H CF₃ HH I-195 4-cyanocinnamyl H CF₃ H H I-196 3-(6-chloro-pyridin-3-yl)-allylH CF₃ H H I-197 3-(4-chlorophenyl)-but-2-enyl H CF₃ H H I-1983-(4-chlorophenyl)-3-fluoro-allyl H CF₃ H H I-1993-chloro-4-fluoro-cinnamyl H CF₃ H H I-200 3,5-dichloro-cinnamyl H CF₃ HH I-201 5-phenyl-penta-2,4-dienyl H CF₃ H H I-2024-isopropyloxycarbonylamino-cinnamyl H CF₃ H H I-2033-naphthalen-2-yl-allyl H CF₃ H H I-2043-(5-trifluoromethyl-pyridin-2-yl)-allyl H CF₃ H H I-2053-(5-chloro-pyridin-2-yl)-allyl H CF₃ H H I-206 3-pyridin-4-yl-allyl HCF₃ H H I-207 3-(2-Chloro-pyridin-4-yl)-allyl H CF₃ H H I-2084-chlorobenzyl H H Cl H I-209 Cinnamyl H H Cl H I-210 4-chlorocinnamyl HH Cl H I-211 4-fluorocinnamyl H H Cl H I-212 4-bromocinnamyl H H Cl HI-213 4-trifluoromethylcinnamyl H H Cl H I-2144-trifluoromethoxycinnamyl H H Cl H I-215 4-pentafluoroethoxycinnamyl HH Cl H I-216 4-methoxycinnamyl H H Cl H I-217 4-ethoxycinnamyl H H Cl HI-218 4-cyanocinnamyl H H Cl H I-219 3-(6-chloro-pyridin-3-yl)-allyl H HCl H I-220 3-(4-chlorophenyl)-but-2-enyl H H Cl H I-2213-(4-chlorophenyl)-3-fluoro-allyl H H Cl H I-2223-chloro-4-fluoro-cinnamyl H H Cl H I-223 3,5-dichloro-cinnamyl H H Cl HI-224 5-phenyl-penta-2,4-dienyl H H Cl H I-2254-isopropyloxycarbonylamino-cinnamyl H H Cl H I-2263-naphthalen-2-yl-allyl H H Cl H I-2273-(5-trifluoromethyl-pyridin-2-yl)-allyl H H Cl H I-2283-(5-chloro-pyridin-2-yl)-allyl H H Cl H I-229 3-pyridin-4-yl-allyl H HCl H I-230 3-(2-Chloro-pyridin-4-yl)-allyl H H Cl H I-231 4-chlorobenzylH H F H I-232 Cinnamyl H H F H I-233 4-chlorocinnamyl H H F H I-2344-fluorocinnamyl H H F H I-235 4-bromocinnamyl H H F H I-2364-trifluoromethylcinnamyl H H F H I-237 4-trifluoromethoxycinnamyl H H FH I-238 4-pentafluoroethoxycinnamyl H H F H I-239 4-methoxycinnamyl H HF H I-240 4-ethoxycinnamyl H H F H I-241 4-cyanocinnamyl H H F H I-2423-(6-chloro-pyridin-3-yl)-allyl H H F H I-2433-(4-chlorophenyl)-but-2-enyl H H F H I-2443-(4-chlorophenyl)-3-fluoro-allyl H H F H I-2453-chloro-4-fluoro-cinnamyl H H F H I-246 3,5-dichloro-cinnamyl H H F HI-247 5-phenyl-penta-2,4-dienyl H H F H I-2484-isopropyloxycarbonylamino-cinnamyl H H F H I-2493-naphthalen-2-yl-allyl H H F H I-2503-(5-trifluoromethyl-pyridin-2-yl)-allyl H H F H I-2513-(5-chloro-pyridin-2-yl)-allyl H H F H I-252 3-pyridin-4-yl-allyl H H FH I-253 3-(2-Chloro-pyridin-4-yl)-allyl H H F H I-254 4-chlorobenzyl H HBr H I-255 Cinnamyl H H Br H I-256 4-chlorocinnamyl H H Br H I-2574-fluorocinnamyl H H Br H I-258 4-bromocinnamyl H H Br H I-2594-trifluoromethylcinnamyl H H Br H I-260 4-trifluoromethoxycinnamyl H HBr H I-261 4-pentafluoroethoxycinnamyl H H Br H I-262 4-methoxycinnamylH H Br H I-263 4-ethoxycinnamyl H H Br H I-264 4-cyanocinnamyl H H Br HI-265 3-(6-chloro-pyridin-3-yl)-allyl H H Br H I-2663-(4-chlorophenyl)-but-2-enyl H H Br H I-2673-(4-chlorophenyl)-3-fluoro-allyl H H Br H I-2683-chloro-4-fluoro-cinnamyl H H Br H I-269 3,5-dichloro-cinnamyl H H Br HI-270 5-phenyl-penta-2,4-dienyl H H Br H I-2714-isopropyloxycarbonylamino-cinnamyl H H Br H I-2723-naphthalen-2-yl-allyl H H Br H I-2733-(5-trifluoromethyl-pyridin-2-yl)-allyl H H Br H I-2743-(5-chloro-pyridin-2-yl)-allyl H H Br H I-275 3-pyridin-4-yl-allyl H HBr H I-276 3-(2-Chloro-pyridin-4-yl)-allyl H H Br H I-277 4-chlorobenzylH H OCF₃ H I-278 Cinnamyl H H OCF₃ H I-279 4-chlorocinnamyl H H OCF₃ HI-280 4-fluorocinnamyl H H OCF₃ H I-281 4-bromocinnamyl H H OCF₃ H I-2824-trifluoromethylcinnamyl H H OCF₃ H I-283 4-trifluoromethoxycinnamyl HH OCF₃ H I-284 4-pentafluoroethoxycinnamyl H H OCF₃ H I-2854-methoxycinnamyl H H OCF₃ H I-286 4-ethoxycinnamyl H H OCF₃ H I-2874-cyanocinnamyl H H OCF₃ H I-288 3-(6-chloro-pyridin-3-yl)-allyl H HOCF₃ H I-289 3-(4-chlorophenyl)-but-2-enyl H H OCF₃ H I-2903-(4-chlorophenyl)-3-fluoro-allyl H H OCF₃ H I-2913-chloro-4-fluoro-cinnamyl H H OCF₃ H I-292 3,5-dichloro-cinnamyl H HOCF₃ H I-293 5-phenyl-penta-2,4-dienyl H H OCF₃ H I-2944-isopropyloxycarbonylamino-cinnamyl H H OCF₃ H I-2953-naphthalen-2-yl-allyl H H OCF₃ H I-2963-(5-trifluoromethyl-pyridin-2-yl)-allyl H H OCF₃ H I-2973-(5-chloro-pyridin-2-yl)-allyl H H OCF₃ H I-298 3-pyridin-4-yl-allyl HH OCF₃ H I-299 3-(2-Chloro-pyridin-4-yl)-allyl H H OCF₃ H I-3004-chlorobenzyl H H CH₃ H I-301 Cinnamyl H H CH₃ H I-302 4-chlorocinnamylH H CH₃ H I-303 4-fluorocinnamyl H H CH₃ H I-304 4-bromocinnamyl H H CH₃H I-305 4-trifluoromethylcinnamyl H H CH₃ H I-3064-trifluoromethoxycinnamyl H H CH₃ H I-307 4-pentafluoroethoxycinnamyl HH CH₃ H I-308 4-methoxycinnamyl H H CH₃ H I-309 4-ethoxycinnamyl H H CH₃H I-310 4-cyanocinnamyl H H CH₃ H I-311 3-(6-chloro-pyridin-3-yl)-allylH H CH₃ H I-312 3-(4-chlorophenyl)-but-2-enyl H H CH₃ H I-3133-(4-chlorophenyl)-3-fluoro-allyl H H CH₃ H I-3143-chloro-4-fluoro-cinnamyl H H CH₃ H I-315 3,5-dichloro-cinnamyl H H CH₃H I-316 5-phenyl-penta-2,4-dienyl H H CH₃ H I-3174-isopropyloxycarbonylamino-cinnamyl H H CH₃ H I-3183-naphthalen-2-yl-allyl H H CH₃ H I-3193-(5-trifluoromethyl-pyridin-2-yl)-allyl H H CH₃ H I-3203-(5-chloro-pyridin-2-yl)-allyl H H CH₃ H I-321 3-pyridin-4-yl-allyl H HCH₃ H I-322 3-(2-Chloro-pyridin-4-yl)-allyl H H CH₃ H I-3234-chlorobenzyl H H CF₃ H I-324 Cinnamyl H H CF₃ H I-325 4-chlorocinnamylH H CF₃ H I-326 4-fluorocinnamyl H H CF₃ H I-327 4-bromocinnamyl H H CF₃H I-328 4-trifluoromethylcinnamyl H H CF₃ H I-3294-trifluoromethoxycinnamyl H H CF₃ H I-330 4-pentafluoroethoxycinnamyl HH CF₃ H I-331 4-methoxycinnamyl H H CF₃ H I-332 4-ethoxycinnamyl H H CF₃H I-333 4-cyanocinnamyl H H CF₃ H I-334 3-(6-chloro-pyridin-3-yl)-allylH H CF₃ H I-335 3-(4-chlorophenyl)-but-2-enyl H H CF₃ H I-3363-(4-chlorophenyl)-3-fluoro-allyl H H CF₃ H I-3373-chloro-4-fluoro-cinnamyl H H CF₃ H I-338 3,5-dichloro-cinnamyl H H CF₃H I-339 5-phenyl-penta-2,4-dienyl H H CF₃ H I-3404-isopropyloxycarbonylamino-cinnamyl H H CF₃ H I-3413-naphthalen-2-yl-allyl H H CF₃ H I-3423-(5-trifluoromethyl-pyridin-2-yl)-allyl H H CF₃ H I-3433-(5-chloro-pyridin-2-yl)-allyl H H CF₃ H I-344 3-pyridin-4-yl-allyl H HCF₃ H I-345 3-(2-Chloro-pyridin-4-yl)-allyl H H CF₃ H I-3464-chlorobenzyl F H H H I-347 Cinnamyl F H H H I-348 4-chlorocinnamyl F HH H I-349 4-fluorocinnamyl F H H H I-350 4-bromocinnamyl F H H H I-3514-trifluoromethylcinnamyl F H H H I-352 4-trifluoromethoxycinnamyl F H HH I-353 4-pentafluoroethoxycinnamyl F H H H I-354 4-methoxycinnamyl F HH H I-355 4-ethoxycinnamyl F H H H I-356 4-cyanocinnamyl F H H H I-3573-(6-chloro-pyridin-3-yl)-allyl F H H H I-3583-(4-chlorophenyl)-but-2-enyl F H H H I-3593-(4-chlorophenyl)-3-fluoro-allyl F H H H I-3603-chloro-4-fluoro-cinnamyl F H H H I-361 3,5-dichloro-cinnamyl F H H HI-362 5-phenyl-penta-2,4-dienyl F H H H I-3634-isopropyloxycarbonylamino-cinnamyl F H H H I-3643-naphthalen-2-yl-allyl F H H H I-3653-(5-trifluoromethyl-pyridin-2-yl)-allyl F H H H I-3663-(5-chloro-pyridin-2-yl)-allyl F H H H I-367 3-pyridin-4-yl-allyl F H HH I-368 3-(2-Chloro-pyridin-4-yl)-allyl F H H H I-369 4-chlorobenzyl ClH H H I-370 Cinnamyl Cl H H H I-371 4-chlorocinnamyl Cl H H H I-3724-fluorocinnamyl Cl H H H I-373 4-bromocinnamyl Cl H H H I-3744-trifluoromethylcinnamyl Cl H H H I-375 4-trifluoromethoxycinnamyl Cl HH H I-376 4-pentafluoroethoxycinnamyl Cl H H H I-377 4-methoxycinnamylCl H H H I-378 4-ethoxycinnamyl Cl H H H I-379 4-cyanocinnamyl Cl H H HI-380 3-(6-chloro-pyridin-3-yl)-allyl Cl H H H I-3813-(4-chlorophenyl)-but-2-enyl Cl H H H I-3823-(4-chlorophenyl)-3-fluoro-allyl Cl H H H I-3833-chloro-4-fluoro-cinnamyl Cl H H H I-384 3,5-dichloro-cinnamyl Cl H H HI-385 5-phenyl-penta-2,4-dienyl Cl H H H I-3864-isopropyloxycarbonylamino-cinnamyl Cl H H H I-3873-naphthalen-2-yl-allyl Cl H H H I-3883-(5-trifluoromethyl-pyridin-2-yl)-allyl Cl H H H I-3893-(5-chloro-pyridin-2-yl)-allyl Cl H H H I-390 3-pyridin-4-yl-allyl Cl HH H I-391 3-(2-Chloro-pyridin-4-yl)-allyl Cl H H H I-392 4-chlorobenzylBr H H H I-393 Cinnamyl Br H H H I-394 4-chlorocinnamyl Br H H H I-3954-fluorocinnamyl Br H H H I-396 4-bromocinnamyl Br H H H I-3974-trifluoromethylcinnamyl Br H H H I-398 4-trifluoromethoxycinnamyl Br HH H I-399 4-pentafluoroethoxycinnamyl Br H H H I-400 4-methoxycinnamylBr H H H I-401 4-ethoxycinnamyl Br H H H I-402 4-cyanocinnamyl Br H H HI-403 3-(6-chloro-pyridin-3-yl)-allyl Br H H H I-4043-(4-chlorophenyl)-but-2-enyl Br H H H I-4053-(4-chlorophenyl)-3-fluoro-allyl Br H H H I-4063-chloro-4-fluoro-cinnamyl Br H H H I-407 3,5-dichloro-cinnamyl Br H H HI-408 5-phenyl-penta-2,4-dienyl Br H H H I-4094-isopropyloxycarbonylamino-cinnamyl Br H H H I-4103-naphthalen-2-yl-allyl Br H H H I-4113-(5-trifluoromethyl-pyridin-2-yl)-allyl Br H H H I-4123-(5-chloro-pyridin-2-yl)-allyl Br H H H I-413 3-pyridin-4-yl-allyl Br HH H I-414 3-(2-Chloro-pyridin-4-yl)-allyl Br H H H I-415 4-chlorobenzylCF₃ H H H I-416 Cinnamyl CF₃ H H H I-417 4-chlorocinnamyl CF₃ H H HI-418 4-fluorocinnamyl CF₃ H H H I-419 4-bromocinnamyl CF₃ H H H I-4204-trifluoromethylcinnamyl CF₃ H H H I-421 4-trifluoromethoxycinnamyl CF₃H H H I-422 4-pentafluoroethoxycinnamyl CF₃ H H H I-4234-methoxycinnamyl CF₃ H H H I-424 4-ethoxycinnamyl CF₃ H H H I-4254-cyanocinnamyl CF₃ H H H I-426 3-(6-chloro-pyridin-3-yl)-allyl CF₃ H HH I-427 3-(4-chlorophenyl)-but-2-enyl CF₃ H H H I-4283-(4-chlorophenyl)-3-fluoro-allyl CF₃ H H H I-4293-chloro-4-fluoro-cinnamyl CF₃ H H H I-430 3,5-dichloro-cinnamyl CF₃ H HH I-431 5-phenyl-penta-2,4-dienyl CF₃ H H H I-4324-isopropyloxycarbonylamino-cinnamyl CF₃ H H H I-4333-naphthalen-2-yl-allyl CF₃ H H H I-4343-(5-trifluoromethyl-pyridin-2-yl)-allyl CF₃ H H H I-4353-(5-chloro-pyridin-2-yl)-allyl CF₃ H H H I-436 3-pyridin-4-yl-allyl CF₃H H H I-437 3-(2-Chloro-pyridin-4-yl)-allyl CF₃ H H H I-4384-chlorobenzyl H H H F I-439 Cinnamyl H H H F I-440 4-chlorocinnamyl H HH F I-441 4-fluorocinnamyl H H H F I-442 4-bromocinnamyl H H H F I-4434-trifluoromethylcinnamyl H H H F I-444 4-trifluoromethoxycinnamyl H H HF I-445 4-pentafluoroethoxycinnamyl H H H F I-446 4-methoxycinnamyl H HH F I-447 4-ethoxycinnamyl H H H F I-448 4-cyanocinnamyl H H H F I-4493-(6-chloro-pyridin-3-yl)-allyl H H H F I-4503-(4-chlorophenyl)-but-2-enyl H H H F I-4513-(4-chlorophenyl)-3-fluoro-allyl H H H F I-4523-chloro-4-fluoro-cinnamyl H H H F I-453 3,5-dichloro-cinnamyl H H H FI-454 5-phenyl-penta-2,4-dienyl H H H F I-4554-isopropyloxycarbonylamino-cinnamyl H H H F I-4563-naphthalen-2-yl-allyl H H H F I-4573-(5-trifluoromethyl-pyridin-2-yl)-allyl H H H F I-4583-(5-chloro-pyridin-2-yl)-allyl H H H F I-459 3-pyridin-4-yl-allyl H H HF I-460 3-(2-Chloro-pyridin-4-yl)-allyl H H H F I-461 4-chlorobenzyl H HH Cl I-462 Cinnamyl H H H Cl I-463 4-chlorocinnamyl H H H Cl I-4644-fluorocinnamyl H H H Cl I-465 4-bromocinnamyl H H H Cl I-4664-trifluoromethylcinnamyl H H H Cl I-467 4-trifluoromethoxycinnamyl H HH Cl I-468 4-pentafluoroethoxycinnamyl H H H Cl I-469 4-methoxycinnamylH H H Cl I-470 4-ethoxycinnamyl H H H Cl I-471 4-cyanocinnamyl H H H ClI-472 3-(6-chloro-pyridin-3-yl)-allyl H H H Cl I-4733-(4-chlorophenyl)-but-2-enyl H H H Cl I-4743-(4-chlorophenyl)-3-fluoro-allyl H H H Cl I-4753-chloro-4-fluoro-cinnamyl H H H Cl I-476 3,5-dichloro-cinnamyl H H H ClI-477 5-phenyl-penta-2,4-dienyl H H H Cl I-4784-isopropyloxycarbonylamino-cinnamyl H H H Cl I-4793-naphthalen-2-yl-allyl H H H Cl I-4803-(5-trifluoromethyl-pyridin-2-yl)-allyl H H H Cl I-4813-(5-chloro-pyridin-2-yl)-allyl H H H Cl I-482 3-pyridin-4-yl-allyl H HH Cl I-483 3-(2-Chloro-pyridin-4-yl)-allyl H H H Cl I-484 4-chlorobenzylH F F H I-485 Cinnamyl H F F H I-486 4-chlorocinnamyl H F F H I-4874-fluorocinnamyl H F F H I-488 4-bromocinnamyl H F F H I-4894-trifluoromethylcinnamyl H F F H I-490 4-trifluoromethoxycinnamyl H F FH I-491 4-pentafluoroethoxycinnamyl H F F H I-492 4-methoxycinnamyl H FF H I-493 4-ethoxycinnamyl H F F H I-494 4-cyanocinnamyl H F F H I-4953-(6-chloro-pyridin-3-yl)-allyl H F F H I-4963-(4-chlorophenyl)-but-2-enyl H F F H I-4973-(4-chlorophenyl)-3-fluoro-allyl H F F H I-4983-chloro-4-fluoro-cinnamyl H F F H I-499 3,5-dichloro-cinnamyl H F F HI-500 5-phenyl-penta-2,4-dienyl H F F H I-5014-isopropyloxycarbonylamino-cinnamyl H F F H I-5023-naphthalen-2-yl-allyl H F F H I-5033-(5-trifluoromethyl-pyridin-2-yl)-allyl H F F H I-5043-(5-chloro-pyridin-2-yl)-allyl H F F H I-505 3-pyridin-4-yl-allyl H F FH I-506 3-(2-Chloro-pyridin-4-yl)-allyl H F F H I-507 4-chlorobenzyl H FCl H I-508 Cinnamyl H F Cl H I-509 4-chlorocinnamyl H F Cl H I-5104-fluorocinnamyl H F Cl H I-511 4-bromocinnamyl H F Cl H I-5124-trifluoromethylcinnamyl H F Cl H I-513 4-trifluoromethoxycinnamyl H FCl H I-514 4-pentafluoroethoxycinnamyl H F Cl H I-515 4-methoxycinnamylH F Cl H I-516 4-ethoxycinnamyl H F Cl H I-517 4-cyanocinnamyl H F Cl HI-518 3-(6-chloro-pyridin-3-yl)-allyl H F Cl H I-5193-(4-chlorophenyl)-but-2-enyl H F Cl H I-5203-(4-chlorophenyl)-3-fluoro-allyl H F Cl H I-5213-chloro-4-fluoro-cinnamyl H F Cl H I-522 3,5-dichloro-cinnamyl H F Cl HI-523 5-phenyl-penta-2,4-dienyl H F Cl H I-5244-isopropyloxycarbonylamino-cinnamyl H F Cl H I-5253-naphthalen-2-yl-allyl H F Cl H I-5263-(5-trifluoromethyl-pyridin-2-yl)-allyl H F Cl H I-5273-(5-chloro-pyridin-2-yl)-allyl H F Cl H I-528 3-pyridin-4-yl-allyl H FCl H I-529 3-(2-Chloro-pyridin-4-yl)-allyl H F Cl H I-530 4-chlorobenzylH Cl F H I-531 Cinnamyl H Cl F H I-532 4-chlorocinnamyl H Cl F H I-5334-fluorocinnamyl H Cl F H I-534 4-bromocinnamyl H Cl F H I-5354-trifluoromethylcinnamyl H Cl F H I-536 4-trifluoromethoxycinnamyl H ClF H I-537 4-pentafluoroethoxycinnamyl H Cl F H I-538 4-methoxycinnamyl HCl F H I-539 4-ethoxycinnamyl H Cl F H I-540 4-cyanocinnamyl H Cl F HI-541 3-(6-chloro-pyridin-3-yl)-allyl H Cl F H I-5423-(4-chlorophenyl)-but-2-enyl H Cl F H I-5433-(4-chlorophenyl)-3-fluoro-allyl H Cl F H I-5443-chloro-4-fluoro-cinnamyl H Cl F H I-545 3,5-dichloro-cinnamyl H Cl F HI-546 5-phenyl-penta-2,4-dienyl H Cl F H I-5474-isopropyloxycarbonylamino-cinnamyl H Cl F H I-5483-naphthalen-2-yl-allyl H Cl F H I-5493-(5-trifluoromethyl-pyridin-2-yl)-allyl H Cl F H I-5503-(5-chloro-pyridin-2-yl)-allyl H Cl F H I-551 3-pyridin-4-yl-allyl H ClF H I-552 3-(2-Chloro-pyridin-4-yl)-allyl H Cl F H I-553 4-chlorobenzylH Cl Cl H I-554 Cinnamyl H Cl Cl H I-555 4-chlorocinnamyl H Cl Cl HI-556 4-fluorocinnamyl H Cl Cl H I-557 4-bromocinnamyl H Cl Cl H I-5584-trifluoromethylcinnamyl H Cl Cl H I-559 4-trifluoromethoxycinnamyl HCl Cl H I-560 4-pentafluoroethoxycinnamyl H Cl Cl H I-5614-methoxycinnamyl H Cl Cl H I-562 4-ethoxycinnamyl H Cl Cl H I-5634-cyanocinnamyl H Cl Cl H I-564 3-(6-chloro-pyridin-3-yl)-allyl H Cl ClH I-565 3-(4-chlorophenyl)-but-2-enyl H Cl Cl H I-5663-(4-chlorophenyl)-3-fluoro-allyl H Cl Cl H I-5673-chloro-4-fluoro-cinnamyl H Cl Cl H I-568 3,5-dichloro-cinnamyl H Cl ClH I-569 5-phenyl-penta-2,4-dienyl H Cl Cl H I-5704-isopropyloxycarbonylamino-cinnamyl H Cl Cl H I-5713-naphthalen-2-yl-allyl H Cl Cl H I-5723-(5-trifluoromethyl-pyridin-2-yl)-allyl H Cl Cl H I-5733-(5-chloro-pyridin-2-yl)-allyl H Cl Cl H I-574 3-pyridin-4-yl-allyl HCl Cl H I-575 3-(2-Chloro-pyridin-4-yl)-allyl H Cl Cl H I-5764-chlorobenzyl H —OCF₂O— H I-577 Cinnamyl H —OCF₂O— H I-5784-chlorocinnamyl H —OCF₂O— H I-579 4-fluorocinnamyl H —OCF₂O— H I-5804-bromocinnamyl H —OCF₂O— H I-581 4-trifluoromethylcinnamyl H —OCF₂O— HI-582 4-trifluoromethoxycinnamyl H —OCF₂O— H I-5834-pentafluoroethoxycinnamyl H —OCF₂O— H I-584 4-methoxycinnamyl H—OCF₂O— H I-585 4-ethoxycinnamyl H —OCF₂O— H I-586 4-cyanocinnamyl H—OCF₂O— H I-587 3-(6-chloro-pyridin-3-yl)-allyl H —OCF₂O— H I-5883-(4-chlorophenyl)-but-2-enyl H —OCF₂O— H I-5893-(4-chlorophenyl)-3-fluoro-allyl H —OCF₂O— H I-5903-chloro-4-fluoro-cinnamyl H —OCF₂O— H I-591 3,5-dichloro-cinnamyl H—OCF₂O— H I-592 5-phenyl-penta-2,4-dienyl H —OCF₂O— H I-5934-isopropyloxycarbonylamino-cinnamyl H —OCF₂O— H I-5943-naphthalen-2-yl-allyl H —OCF₂O— H I-5953-(5-trifluoromethyl-pyridin-2-yl)-allyl H —OCF₂O— H I-5963-(5-chloro-pyridin-2-yl)-allyl H —OCF₂O— H I-597 3-pyridin-4-yl-allyl H—OCF₂O— H I-598 3-(2-Chloro-pyridin-4-yl)-allyl H —OCF₂O— H I-5994-chlorobenzyl H —C₄H₄— H I-600 Cinnamyl H —C₄H₄— H I-6014-chlorocinnamyl H —C₄H₄— H I-602 4-fluorocinnamyl H —C₄H₄— H I-6034-bromocinnamyl H —C₄H₄— H I-604 4-trifluoromethylcinnamyl H —C₄H₄— HI-605 4-trifluoromethoxycinnamyl H —C₄H₄— H I-6064-pentafluoroethoxycinnamyl H —C₄H₄— H I-607 4-methoxycinnamyl H —C₄H₄—H I-608 4-ethoxycinnamyl H —C₄H₄— H I-609 4-cyanocinnamyl H —C₄H₄— HI-610 3-(6-chloro-pyridin-3-yl)-allyl H —C₄H₄— H I-6113-(4-chlorophenyl)-but-2-enyl H —C₄H₄— H I-6123-(4-chlorophenyl)-3-fluoro-allyl H —C₄H₄— H I-6133-chloro-4-fluoro-cinnamyl H —C₄H₄— H I-614 3,5-dichloro-cinnamyl H—C₄H₄— H I-615 5-phenyl-penta-2,4-dienyl H —C₄H₄— H I-6164-isopropyloxycarbonylamino-cinnamyl H —C₄H₄— H I-6173-naphthalen-2-yl-allyl H —C₄H₄— H I-6183-(5-trifluoromethyl-pyridin-2-yl)-allyl H —C₄H₄— H I-6193-(5-chloro-pyridin-2-yl)-allyl H —C₄H₄— H I-620 3-pyridin-4-yl-allyl H—C₄H₄— H I-621 3-(2-Chloro-pyridin-4-yl)-allyl H —C₄H₄— H I-6224-chlorobenzyl Cl H Cl H I-623 Cinnamyl Cl H Cl H I-624 4-chlorocinnamylCl H Cl H I-625 4-fluorocinnamyl Cl H Cl H I-626 4-bromocinnamyl Cl H ClH I-627 4-trifluoromethylcinnamyl Cl H Cl H I-6284-trifluoromethoxycinnamyl Cl H Cl H I-629 4-pentafluoroethoxycinnamylCl H Cl H I-630 4-methoxycinnamyl Cl H Cl H I-631 4-ethoxycinnamyl Cl HCl H I-632 4-cyanocinnamyl Cl H Cl H I-6333-(6-chloro-pyridin-3-yl)-allyl Cl H Cl H I-6343-(4-chlorophenyl)-but-2-enyl Cl H Cl H I-6353-(4-chlorophenyl)-3-fluoro-allyl Cl H Cl H I-6363-chloro-4-fluoro-cinnamyl Cl H Cl H I-637 3,5-dichloro-cinnamyl Cl H ClH I-638 5-phenyl-penta-2,4-dienyl Cl H Cl H I-6394-isopropyloxycarbonylamino-cinnamyl Cl H Cl H I-6403-naphthalen-2-yl-allyl Cl H Cl H I-6413-(5-trifluoromethyl-pyridin-2-yl)-allyl Cl H Cl H I-6423-(5-chloro-pyridin-2-yl)-allyl Cl H Cl H I-643 3-pyridin-4-yl-allyl ClH Cl H I-644 3-(2-Chloro-pyridin-4-yl)-allyl Cl H Cl H I-6454-chlorobenzyl Cl Cl H H I-646 Cinnamyl Cl Cl H H I-647 4-chlorocinnamylCl Cl H H I-648 4-fluorocinnamyl Cl Cl H H I-649 4-bromocinnamyl Cl Cl HH I-650 4-trifluoromethylcinnamyl Cl Cl H H I-6514-trifluoromethoxycinnamyl Cl Cl H H I-652 4-pentafluoroethoxycinnamylCl Cl H H I-653 4-methoxycinnamyl Cl Cl H H I-654 4-ethoxycinnamyl Cl ClH H I-655 4-cyanocinnamyl Cl Cl H H I-6563-(6-chloro-pyridin-3-yl)-allyl Cl Cl H H I-6573-(4-chlorophenyl)-but-2-enyl Cl Cl H H I-6583-(4-chlorophenyl)-3-fluoro-allyl Cl Cl H H I-6593-chloro-4-fluoro-cinnamyl Cl Cl H H I-660 3,5-dichloro-cinnamyl Cl Cl HH I-661 5-phenyl-penta-2,4-dienyl Cl Cl H H I-6624-isopropyloxycarbonylamino-cinnamyl Cl Cl H H I-6633-naphthalen-2-yl-allyl Cl Cl H H I-6643-(5-trifluoromethyl-pyridin-2-yl)-allyl Cl Cl H H I-6653-(5-chloro-pyridin-2-yl)-allyl Cl Cl H H I-666 3-pyridin-4-yl-allyl ClCl H H I-667 3-(2-Chloro-pyridin-4-yl)-allyl Cl Cl H H I-6684-chlorobenzyl H Cl H Cl I-669 Cinnamyl H Cl H Cl I-670 4-chlorocinnamylH Cl H Cl I-671 4-fluorocinnamyl H Cl H Cl I-672 4-bromocinnamyl H Cl HCl I-673 4-trifluoromethylcinnamyl H Cl H Cl I-6744-trifluoromethoxycinnamyl H Cl H Cl I-675 4-pentafluoroethoxycinnamyl HCl H Cl I-676 4-methoxycinnamyl H Cl H Cl I-677 4-ethoxycinnamyl H Cl HCl I-678 4-cyanocinnamyl H Cl H Cl I-679 3-(6-chloro-pyridin-3-yl)-allylH Cl H Cl I-680 3-(4-chlorophenyl)-but-2-enyl H Cl H Cl I-6813-(4-chlorophenyl)-3-fluoro-allyl H Cl H Cl I-6823-chloro-4-fluoro-cinnamyl H Cl H Cl I-683 3,5-dichloro-cinnamyl H Cl HCl I-684 5-phenyl-penta-2,4-dienyl H Cl H Cl I-6854-isopropyloxycarbonylamino-cinnamyl H Cl H Cl I-6863-naphthalen-2-yl-allyl H Cl H Cl I-6873-(5-trifluoromethyl-pyridin-2-yl)-allyl H Cl H Cl I-6883-(5-chloro-pyridin-2-yl)-allyl H Cl H Cl I-689 3-pyridin-4-yl-allyl HCl H Cl I-690 3-(2-Chloro-pyridin-4-yl)-allyl H Cl H Cl I-6914-chlorobenzyl H F H F I-692 Cinnamyl H F H F I-693 4-chlorocinnamyl H FH F I-694 4-fluorocinnamyl H F H F I-695 4-bromocinnamyl H F H F I-6964-trifluoromethylcinnamyl H F H F I-697 4-trifluoromethoxycinnamyl H F HF I-698 4-pentafluoroethoxycinnamyl H F H F I-699 4-methoxycinnamyl H FH F I-700 4-ethoxycinnamyl H F H F I-701 4-cyanocinnamyl H F H F I-7023-(6-chloro-pyridin-3-yl)-allyl H F H F I-7033-(4-chlorophenyl)-but-2-enyl H F H F I-7043-(4-chlorophenyl)-3-fluoro-allyl H F H F I-7053-chloro-4-fluoro-cinnamyl H F H F I-706 3,5-dichloro-cinnamyl H F H FI-707 5-phenyl-penta-2,4-dienyl H F H F I-7084-isopropyloxycarbonylamino-cinnamyl H F H F I-7093-naphthalen-2-yl-allyl H F H F I-7103-(5-trifluoromethyl-pyridin-2-yl)-allyl H F H F I-7113-(5-chloro-pyridin-2-yl)-allyl H F H F I-712 3-pyridin-4-yl-allyl H F HF I-713 3-(2-Chloro-pyridin-4-yl)-allyl H F H F I-714 4-chlorobenzyl F HF H I-715 Cinnamyl F H F H I-716 4-chlorocinnamyl F H F H I-7174-fluorocinnamyl F H F H I-718 4-bromocinnamyl F H F H I-7194-trifluoromethylcinnamyl F H F H I-720 4-trifluoromethoxycinnamyl F H FH I-721 4-pentafluoroethoxycinnamyl F H F H I-722 4-methoxycinnamyl F HF H I-723 4-ethoxycinnamyl F H F H I-724 4-cyanocinnamyl F H F H I-7253-(6-chloro-pyridin-3-yl)-allyl F H F H I-7263-(4-chlorophenyl)-but-2-enyl F H F H I-7273-(4-chlorophenyl)-3-fluoro-allyl F H F H I-7283-chloro-4-fluoro-cinnamyl F H F H I-729 3,5-dichloro-cinnamyl F H F HI-730 5-phenyl-penta-2,4-dienyl F H F H I-7314-isopropyloxycarbonylamino-cinnamyl F H F H I-7323-naphthalen-2-yl-allyl F H F H I-7333-(5-trifluoromethyl-pyridin-2-yl)-allyl F H F H I-7343-(5-chloro-pyridin-2-yl)-allyl F H F H I-735 3-pyridin-4-yl-allyl F H FH I-736 3-(2-Chloro-pyridin-4-yl)-allyl F H F H I-737 4-chlorobenzyl F FH H I-738 Cinnamyl F F H H I-739 4-chlorocinnamyl F F H H I-7404-fluorocinnamyl F F H H I-741 4-bromocinnamyl F F H H I-7424-trifluoromethylcinnamyl F F H H I-743 4-trifluoromethoxycinnamyl F F HH I-744 4-pentafluoroethoxycinnamyl F F H H I-745 4-methoxycinnamyl F FH H I-746 4-ethoxycinnamyl F F H H I-747 4-cyanocinnamyl F F H H I-7483-(6-chloro-pyridin-3-yl)-allyl F F H H I-7493-(4-chlorophenyl)-but-2-enyl F F H H I-7503-(4-chlorophenyl)-3-fluoro-allyl F F H H I-7513-chloro-4-fluoro-cinnamyl F F H H I-752 3,5-dichloro-cinnamyl F F H HI-753 5-phenyl-penta-2,4-dienyl F F H H I-7544-isopropyloxycarbonylamino-cinnamyl F F H H I-7553-naphthalen-2-yl-allyl F F H H I-7563-(5-trifluoromethyl-pyridin-2-yl)-allyl F F H H I-7573-(5-chloro-pyridin-2-yl)-allyl F F H H I-758 3-pyridin-4-yl-allyl F F HH I-759 3-(2-Chloro-pyridin-4-yl)-allyl F F H H I-760 4-chlorobenzyl ClF H H I-761 Cinnamyl Cl F H H I-762 4-chlorocinnamyl Cl F H H I-7634-fluorocinnamyl Cl F H H I-764 4-bromocinnamyl Cl F H H I-7654-trifluoromethylcinnamyl Cl F H H I-766 4-trifluoromethoxycinnamyl Cl FH H I-767 4-pentafluoroethoxycinnamyl Cl F H H I-768 4-methoxycinnamylCl F H H I-769 4-ethoxycinnamyl Cl F H H I-770 4-cyanocinnamyl Cl F H HI-771 3-(6-chloro-pyridin-3-yl)-allyl Cl F H H I-7723-(4-chlorophenyl)-but-2-enyl Cl F H H I-7733-(4-chlorophenyl)-3-fluoro-allyl Cl F H H I-7743-chloro-4-fluoro-cinnamyl Cl F H H I-775 3,5-dichloro-cinnamyl Cl F H HI-776 5-phenyl-penta-2,4-dienyl Cl F H H I-7774-isopropyloxycarbonylamino-cinnamyl Cl F H H I-7783-naphthalen-2-yl-allyl Cl F H H I-7793-(5-trifluoromethyl-pyridin-2-yl)-allyl Cl F H H I-7803-(5-chloro-pyridin-2-yl)-allyl Cl F H H I-781 3-pyridin-4-yl-allyl Cl FH H I-782 3-(2-Chloro-pyridin-4-yl)-allyl Cl F H H

Table II provides 782 compounds of formula Ib

wherein each Ra is H, p is 1, q is 2 and the values of R⁸, R^(4a),R^(4b), R^(4c) and R^(4d) are given in Table 1.

Table III provides 782 compounds of formula Ic

wherein each Ra is H, p is 1, q is 2 and the values of R⁸, R^(4a),R^(4b), R^(4c) and R^(4d) are given in Table 1

Table IV provides 782 compounds of formula Id

wherein each Ra is H, p is 1, q is 2 and the values of R⁸, R^(4a),R^(4b), R^(4c) and R^(4d) are given in Table 1

Table V provides 782 compounds of formula Ie

wherein each Ra is H, p is 1, q is 2 and the values of R⁸, R^(4a),R^(4b), R^(4c) and R^(4d) are given in Table 1

Table VI provides 782 compounds of formula If

wherein each Ra is H, p is 1, q is 2 and the values of R⁸, R^(4a),R^(4b), R^(4c) and R^(4d) are given in Table 1

Table VII provides 782 compounds of formula Ig

wherein each Ra is H, p is 1, q is 2 and the values of R⁸, R^(4a),R^(4b), R^(4c) and R^(4d) are given in Table 1.

Table VIII provides 782 compounds of formula Ih

wherein each Ra is H, p is 1, q is 2 and the values of R⁸, R^(4a),R^(4b), R^(4c) and R^(4d) are given in Table 1

Table IX provides 782 compounds of formula Ii

wherein each Ra is H, p is 1, q is 2 and the values of R⁸, R^(4a),R^(4b), R^(4c) and R^(4d) are given in Table 1.

Table X provides 782 compounds of formula Ij

wherein each Ra is H, p is 1, q is 2 and the values of R⁸, R^(4a),R^(4b), R^(4c) and R^(4d) are given in Table 1.

Table XI provides 782 compounds of formula Ik

wherein each Ra is H, p is 1, q is 2 and the values of R⁸, R^(4a),R^(4b), R^(4c) and R^(4d) are given in Table 1.

Table XII provides 782 compounds of formula II

wherein each Ra is H, p is 1, q is 2 and the values of R⁸, R^(4a),R^(4b), R^(4c) and R^(4d) are given in Table 1.

Table XIII provides 782 compounds of formula Im

wherein each Ra is H, p is 1, q is 2 and the values of R⁸, R^(4a),R^(4b), R^(4c) and R^(4d) are given in Table 1.

Table XIV provides 782 compounds of formula In

wherein each Ra is H, p is 1, q is 2 and the values of R⁸, R^(4a),R^(4b), R^(4c) and R^(4d) are given in Table 1.

Table XV provides 782 compounds of formula Io

wherein each Ra is H, p is 1, q is 2 and the values of R⁸, R^(4a),R^(4b), R^(4c) and R^(4d) are given in Table 1.

Table XVI provides 782 compounds of formula Ip

wherein each Ra is H, p is 1, q is 2 and the values of R⁸, R^(4a),R^(4b), R^(4c) and R^(4d) are given in Table 1.

Table XVII provides 782 compounds of formula Iq

wherein each Ra is H, p is 1, q is 2 and the values of R⁸, R^(4a),R^(4b), R^(4c) and R^(4d) are given in Table 1.

Table XVIII provides 782 compounds of formula Ir

wherein each Ra is H, p is 1, q is 2 and the values of R⁸, R^(4a),R^(4b), R^(4c) and R^(4d) are given in Table 1.

Table XIX provides 782 compounds of formula Is

wherein each Ra is H, p is 1, q is 2 and the values of R⁸, R^(4a),R^(4b), R^(4c) and R^(4d) are given in Table 1.

Table XX provides 782 compounds of formula It

wherein each Ra is H, p is 1, q is 2 and the values of R⁸, R^(4a),R^(4b), R^(4c) and R^(4d) are given in Table 1.

Table XXI provides 782 compounds of formula Iu

wherein each Ra is H, p is 1, q is 2 and the values of R⁸, R^(4a),R^(4b), R^(4c) and R^(4d) are given in Table 1.

Table XXII provides 782 compounds of formula Iv

wherein each Ra is H, p is 1, q is 2 and the values of R⁸, R^(4a),R^(4b), R^(4c) and R^(4d) are given in Table 1.

Table XXIII provides 782 compounds of formula Iw

wherein each Ra is H, p is 1, q is 2 and the values of R⁸, R^(4a),R^(4b), R^(4c) and R^(4d) are given in Table 1.

Table XXIV provides 782 compounds of formula Ix

wherein each Ra is H, p is 1, q is 2 and the values of R⁸, R^(4a),R^(4b), R^(4c) and R^(4d) are given in Table 1.

Table XXV provides 782 compounds of formula Iy

wherein each Ra is H, p is 1, q is 2 and the values of R⁸, R^(4a),R^(4b), R^(4c) and R^(4d) are given in Table 1.

Table XXVI provides 782 compounds of formula Iz

wherein each Ra is H, p is 1, q is 2 and the values of R⁸, R^(4a),R^(4b), R^(4c) and R^(4d) are given in Table 1.

Table XXVII provides 782 compounds of formula Iaa

wherein each Ra is H, p is 1, q is 2 and the values of R⁸, R^(4a),R^(4b), R^(4c) and R^(4d) are given in Table 1.

Table XXVIII provides 782 compounds of formula Iab

wherein each Ra is H, p is 1, q is 2 and the values of R⁸, R^(4a),R^(4b), R^(4c) and R^(4d) are given in Table 1.

Table XXIX provides 782 compounds of formula Iac

wherein each Ra is H, p is 1, q is 2 and the values of R⁸, R^(4a),R^(4b), R^(4c) and R^(4d) are given in Table 1.

Table XXX provides 782 compounds of formula Iad

wherein each Ra is H, p is 1, q is 2 and the values of R⁸, R^(4a),R^(4b), R^(4c) and R^(4d) are given in Table 1.

Table XXXI provides 782 compounds of formula Iae

wherein each Ra is H, p is 1, q is 2 and the values of R⁸, R^(4a),R^(4b), R^(4c) and R^(4d) are given in Table 1.

Table XXXII provides 782 compounds of formula Iaf

wherein each Ra is H, p is 1, q is 2 and the values of R⁸, R^(4a),R^(4b), R^(4c) and R^(4d) are given in Table 1.

Table XXXIII provides 782 compounds of formula Iag

wherein each Ra is H, p is 1, q is 2 and the values of R⁸, R^(4a),R^(4b), R^(4c) and R^(4d) are given in Table 1.

Table XXXIV provides 782 compounds of formula Iah

wherein each Ra is H, p is 1, q is 2 and the values of R⁸, R^(4a),R^(4b), R^(4c) and R^(4d) are given in Table 1.

Table XXXV provides 782 compounds of formula Iai

wherein each Ra is H, p is 1, q is 2 and the values of R⁸, R^(4a),R^(4b), R^(4c) and R^(4d) are given in Table 1.

Table XXXVI provides 782 compounds of formula Iaj

wherein each Ra is H, p is 1, q is 2 and the values of R⁸, R^(4a),R^(4b), R^(4c) and R^(4d) are given in Table 1.

Table XXXVII provides 782 compounds of formula Iak

wherein each Ra is H, p is 1, q is 2 and the values of R⁸, R^(4a),R^(4b), R^(4c) and R^(4d) are given in Table 1.

Table XXXVIII provides 782 compounds of formula Ial

wherein each Ra is H, p is 1, q is 2 and the values of R⁸, R^(4a),R^(4b), R^(4c) and R^(4d) are given in Table 1.

Table XXXIX provides 782 compounds of formula Iam

wherein each Ra is H, p is 1, q is 2 and the values of R⁸, R^(4a),R^(4b), R^(4c) and R^(4d) are given in Table 1.

Table XL provides 782 compounds of formula Ian

wherein each Ra is H, p is 1, q is 2 and the values of R⁸, R^(4a),R^(4b), R^(4c) and R^(4d) are given in Table 1.

Table XLI provides 782 compounds of formula Iao

wherein each Ra is H, p is 1, q is 2 and the values of R⁸, R^(4a),R^(4b), R^(4c) and R^(4d) are given in Table 1.

Table XLII provides 782 compounds of formula Iap

wherein each Ra is H, p is 1, q is 2 and the values of R⁸, R^(4a),R^(4b), R^(4c) and R^(4d) are given in Table 1.

Table XLIII provides 782 compounds of formula Iaq

wherein each Ra is H, p is 1, q is 2 and the values of R⁸, R^(4a),R^(4b), R^(4c) and R^(4d) are given in Table 1.

Table XLIV provides 782 compounds of formula Iar

wherein each Ra is H, p is 1, q is 2 and the values of R⁸, R^(4a),R^(4b), R^(4c) and R^(4d) are given in Table 1.

Table XLV provides 782 compounds of formula Ias

wherein each Ra is H, p is 1, q is 2 and the values of R⁸, R^(4a),R^(4b), R^(4c) and R^(4d) are given in Table 1.

Table XLVI provides 782 compounds of formula Iat

wherein each Ra is H, p is 1, q is 2 and the values of R⁸, R^(4a),R^(4b), R^(4c) and R^(4d) are given in Table 1.

Table XLVII provides 782 compounds of formula Iau

wherein each Ra is H, p is 1, q is 2 and the values of R⁸, R^(4a),R^(4b), R^(4c) and R^(4d) are given in Table 1.

Table XLVIII provides 782 compounds of formula Iav

wherein each Ra is H, p is 1, q is 2 and the values of R⁸, R^(4a),R^(4b), R^(4c) and R^(4d) are given in Table 1.

Table XLIX provides 782 compounds of formula Iaw

wherein each Ra is H, p is 1, q is 2 and the values of R⁸, R^(4a),R^(4b), R^(4c) and R^(4d) are given in Table 1.

Table L provides 782 compounds of formula Iax

wherein each Ra is H, p is 1, q is 2 and the values of R⁸, R^(4a),R^(4b), R^(4c) and R^(4d) are given in Table 1.

Table LI provides 782 compounds of formula Iay

wherein each Ra is H, p is 1, q is 2 and the values of R⁸, R^(4a),R^(4b), R^(4c) and R^(4d) are given in Table 1.

Table LII provides 782 compounds of formula Iaz

wherein each Ra is H, p is 1, q is 2 and the values of R⁸, R^(4a),R^(4b), R^(4c) and R^(4d) are given in Table 1.

Table LIII provides 782 compounds of formula Iba

wherein each Ra is H, p is 1, q is 2 and the values of R⁸, R^(4a),R^(4b), R^(4c) and R^(4d) are given in Table 1.

Table LIV provides 782 compounds of formula Ibb

wherein each Ra is H, p is 1, q is 2 and the values of R⁸, R^(4a),R^(4b), R^(4c) and R^(4d) are given in Table 1.

Table LV provides 782 compounds of formula Ibc

wherein each Ra is H, p is 1, q is 2 and the values of R⁸, R^(4a),R^(4b), R^(4c) and R^(4d) are given in Table 1.

Table LVI provides 782 compounds of formula Ibd

wherein each Ra is H, p is 1, q is 2 and the values of R⁸, R^(4a),R^(4b), R^(4c) and R^(4d) are given in Table 1.

Table LVII provides 782 compounds of formula Ibe

wherein each Ra is H, p is 1, q is 2 and the values of R⁸, R^(4a),R^(4b), R^(4c) and R^(4d) are given in Table 1.

Table LVIII provides 782 compounds of formula Ibf

wherein each Ra is H, p is 1, q is 2 and the values of R⁸, R^(4a),R^(4b), R^(4c) and R^(4d) are given in Table 1.

Table LIX provides 782 compounds of formula Ibg

wherein each Ra is H, p is 1, q is 2 and the values of R⁸, R^(4a),R^(4b), R^(4c) and R^(4d) are given in Table 1.

Table LX provides 782 compounds of formula Ibh

wherein each Ra is H, p is 1, q is 2 and the values of R⁸, R^(4a),R^(4b), R^(4c) and R^(4d) are given in Table 1.

Table LXI provides 782 compounds of formula Ibi

wherein each Ra is H, p is 1, q is 2 and the values of R⁸, R^(4a),R^(4b), R^(4c) and R^(4d) are given in Table 1.

Table LXII provides 782 compounds of formula Ibj

wherein each Ra is H, p is 1, q is 2 and the values of R⁸, R^(4a),R^(4b), R^(4c) and R^(4d) are given in Table 1.

Table LXIII provides 782 compounds of formula Ibk

wherein each Ra is H, p is 1, q is 2 and the values of R⁸, R^(4a),R^(4b), R^(4c) and R^(4d) are given in Table 1.

Table LXIV provides 782 compounds of formula Ibl

wherein each Ra is H, p is 1, q is 2 and the values of R⁸, R^(4a),R^(4b), R^(4c) and R^(4d) are given in Table 1.

Table LXV provides 782 compounds of formula Ibm

wherein each Ra is H, p is 1, q is 2 and the values of R⁸, R^(4a),R^(4b), R^(4c) and R^(4d) are given in Table 1.

Table LXVI provides 782 compounds of formula Ibn

wherein each Ra is H, p is 1, q is 2 and the values of R⁸, R^(4a),R^(4b), R^(4c) and R^(4d) are given in Table 1.

Table LXVII provides 782 compounds of formula Ibo

wherein each Ra is H, p is 1, q is 2 and the values of R⁸, R^(4a),R^(4b), R^(4c) and R^(4d) are given in Table 1.

Table LXVIII provides 782 compounds of formula Ibp

wherein each Ra is H, p is 1, q is 2 and the values of R⁸, R^(4a),R^(4b), R^(4c) and R^(4d) are given in Table 1.

Table LXIX provides 782 compounds of formula Ia wherein each Ra is H, pis 1, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d) aregiven in Table 1.

Table LXX provides 782 compounds of formula Ib wherein each Ra is H, pis 1, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d) aregiven in Table 1.

Table LXXI provides 782 compounds of formula Ic wherein each Ra is H, pis 1, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d) aregiven in Table 1.

Table LXXII provides 782 compounds of formula Id wherein each Ra is H, pis 1, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d) aregiven in Table 1.

Table LXXIII provides 782 compounds of formula Ie wherein each Ra is H,p is 1, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d)are given in Table 1.

Table LXXIV provides 782 compounds of formula If wherein each Ra is H, pis 1, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d) aregiven in Table 1.

Table LXXV provides 782 compounds of formula Ig wherein each Ra is H, pis 1, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d) aregiven in Table 1.

Table LXXVI provides 782 compounds of formula Ih wherein each Ra is H, pis 1, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d) aregiven in Table 1.

Table LXXVII provides 782 compounds of formula Ii wherein each Ra is H,p is 1, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d)are given in Table 1.

Table LXXVIII provides 782 compounds of formula Ij wherein each Ra is H,p is 1, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d)are given in Table 1.

Table LXXXIX provides 782 compounds of formula Ik wherein each Ra is H,p is 1, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d)are given in Table 1.

Table LXXX provides 782 compounds of formula II wherein each Ra is H, pis 1, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d) aregiven in Table 1.

Table LXXXI provides 782 compounds of formula Im wherein each Ra is H, pis 1, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d) aregiven in Table 1.

Table LXXXII provides 782 compounds of formula In wherein each Ra is H,p is 1, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d)are given in Table 1.

Table LXXXIII provides 782 compounds of formula Io wherein each Ra is H,p is 1, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d)are given in Table 1.

Table LXXXIV provides 782 compounds of formula Ip wherein each Ra is H,p is 1, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d)are given in Table 1.

Table LXXXV provides 782 compounds of formula Iq wherein each Ra is H, pis 1, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d) aregiven in Table 1.

Table LXXXVI provides 782 compounds of formula Ir wherein each Ra is H,p is 1, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d)are given in Table 1.

Table LXXXVII provides 782 compounds of formula Is wherein each Ra is H,p is 1, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d)are given in Table 1.

Table LXXXVIII provides 782 compounds of formula It wherein each Ra isH, p is 1, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) andR^(4d) are given in Table 1.

Table LXXXIX provides 782 compounds of formula Iu wherein each Ra is H,p is 1, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d)are given in Table 1.

Table XC provides 782 compounds of formula Iv wherein each Ra is H, p is1, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d) aregiven in Table 1.

Table XCI provides 782 compounds of formula Iw wherein each Ra is H, pis 1, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d) aregiven in Table 1.

Table XCII provides 782 compounds of formula Ix wherein each Ra is H, pis 1, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d) aregiven in Table 1.

Table XCIII provides 782 compounds of formula Iy wherein each Ra is H, pis 1, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d) aregiven in Table 1.

Table XCIV provides 782 compounds of formula Iz wherein each Ra is H, pis 1, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d) aregiven in Table 1.

Table XCV provides 782 compounds of formula Iaa wherein each Ra is H, pis 1, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d) aregiven in Table 1.

Table XCVI provides 782 compounds of formula Iab wherein each Ra is H, pis 1, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d) aregiven in Table 1.

Table XCVII provides 782 compounds of formula Iac wherein each Ra is H,p is 1, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d)are given in Table 1.

Table XCVIII provides 782 compounds of formula Iad wherein each Ra is H,p is 1, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d)are given in Table 1.

Table XCIX provides 782 compounds of formula Iae wherein each Ra is H, pis 1, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d) aregiven in Table 1.

Table C provides 782 compounds of formula Iaf wherein each Ra is H, p is1, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d) aregiven in Table 1.

Table CI provides 782 compounds of formula Iag wherein each Ra is H, pis 1, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d) aregiven in Table 1.

Table CII provides 782 compounds of formula Iah wherein each Ra is H, pis 1, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d) aregiven in Table 1.

Table CIII provides 782 compounds of formula Iai wherein each Ra is H, pis 1, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d) aregiven in Table 1.

Table CIV provides 782 compounds of formula Iaj wherein each Ra is H, pis 1, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d) aregiven in Table 1.

Table CV provides 782 compounds of formula Iak wherein each Ra is H, pis 1, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d) aregiven in Table 1.

Table CVI provides 782 compounds of formula Ial wherein each Ra is H, pis 1, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d) aregiven in Table 1.

Table CVII provides 782 compounds of formula Iam wherein each Ra is H, pis 1, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d) aregiven in Table 1.

Table CVIII provides 782 compounds of formula Ian wherein each Ra is H,p is 1, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d)are given in Table 1.

Table CIX provides 782 compounds of formula Iao wherein each Ra is H, pis 1, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d) aregiven in Table 1.

Table CX provides 782 compounds of formula Iap wherein each Ra is H, pis 1, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d) aregiven in Table 1.

Table CXI provides 782 compounds of formula Iaq wherein each Ra is H, pis 1, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d) aregiven in Table 1.

Table CXII provides 782 compounds of formula Iar wherein each Ra is H, pis 1, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d) aregiven in Table 1.

Table CXIII provides 782 compounds of formula Ias wherein each Ra is H,p is 1, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d)are given in Table 1.

Table CXIV provides 782 compounds of formula Iat wherein each Ra is H, pis 1, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d) aregiven in Table 1.

Table CXV provides 782 compounds of formula Iau wherein each Ra is H, pis 1, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d) aregiven in Table 1.

Table CXVI provides 782 compounds of formula Iav wherein each Ra is H, pis 1, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d) aregiven in Table 1.

Table CXVII provides 782 compounds of formula Iaw wherein each Ra is H,p is 1, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d)are given in Table 1.

Table CXVIII provides 782 compounds of formula Iax wherein each Ra is H,p is 1, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d)are given in Table 1.

Table CXIX provides 782 compounds of formula Iay wherein each Ra is H, pis 1, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d) aregiven in Table 1.

Table CXX provides 782 compounds of formula Iaz wherein each Ra is H, pis 1, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d) aregiven in Table 1.

Table CXXI provides 782 compounds of formula Iba wherein each Ra is H, pis 1, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d) aregiven in Table 1.

Table CXXII provides 782 compounds of formula Ibb wherein each Ra is H,p is 1, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d)are given in Table 1.

Table CXXIII provides 782 compounds of formula Ibc wherein each Ra is H,p is 1, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d)are given in Table 1.

Table CXXIV provides 782 compounds of formula Ibd wherein each Ra is H,p is 1, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d)are given in Table 1.

Table CXXV provides 782 compounds of formula Ibe wherein each Ra is H, pis 1, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d) aregiven in Table 1.

Table CXXVI provides 782 compounds of formula Ibf wherein each Ra is H,p is 1, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d)are given in Table 1.

Table CXXVII provides 782 compounds of formula Ibg wherein each Ra is H,p is 1, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d)are given in Table 1.

Table CXXIII provides 782 compounds of formula Ibh wherein each Ra is H,p is 1, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d)are given in Table 1.

Table CXXIX provides 782 compounds of formula Ibi wherein each Ra is H,p is 1, q q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d)are given in Table 1.

Table CXXX provides 782 compounds of formula Ibj wherein each Ra is H, pis 1, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d) aregiven in Table 1.

Table CXXXI provides 782 compounds of formula Ibk wherein each Ra is H,p is 1, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d)are given in Table 1.

Table CVXXII provides 782 compounds of formula Ibl wherein each Ra is H,p is 1, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d)are given in Table 1.

Table CXXXIII provides 782 compounds of formula Ibm wherein each Ra isH, p is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d) aregiven in Table 1.

Table CXXXIV provides 782 compounds of formula Ibn wherein each Ra is H,p is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d) are givenin Table 1.

Table CXXXV provides 782 compounds of formula Ibo wherein each Ra is H,p is 1, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d)are given in Table 1.

Table CXXXVI provides 782 compounds of formula Ibp wherein each Ra is H,p is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d) are givenin Table 1.

Table CXXXVII provides 782 compounds of formula Ia wherein each Ra is H,p is 2, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d)are given in Table 1.

Table CXXXVIII provides 782 compounds of formula Ib wherein each Ra isH, p is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d) aregiven in Table 1.

Table CXXXIX provides 782 compounds of formula Ic wherein each Ra is H,p is 2, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d)are given in Table 1.

Table CXL provides 782 compounds of formula Id wherein each Ra is H, pis 2, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d) aregiven in Table 1.

Table CXLI provides 782 compounds of formula Ie wherein each Ra is H, pis 2, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d) aregiven in Table 1.

Table CXLII provides 782 compounds of formula If wherein each Ra is H, pis 2, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d) aregiven in Table 1.

Table CXLIII provides 782 compounds of formula Ig wherein each Ra is H,p is 2, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d)are given in Table 1.

Table CXLIV provides 782 compounds of formula Ih wherein each Ra is H, pis 2, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d) aregiven in Table 1.

Table CXLV provides 782 compounds of formula Ii wherein each Ra is H, pis 2, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d) aregiven in Table 1.

Table CXLVI provides 782 compounds of formula Ij wherein each Ra is H, pis 2, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d) aregiven in Table 1.

Table CXLVII provides 782 compounds of formula Ik wherein each Ra is H,p is 2, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d)are given in Table 1.

Table CXLVIII provides 782 compounds of formula II wherein each Ra is H,p is 2, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d)are given in Table 1.

Table CXLIX provides 782 compounds of formula Im wherein each Ra is H, pis 2, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d) aregiven in Table 1.

Table CL provides 782 compounds of formula In wherein each Ra is H, p is2, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d) aregiven in Table 1.

Table CLI provides 782 compounds of formula Io wherein each Ra is H, pis 2, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d) aregiven in Table 1.

Table CLII provides 782 compounds of formula Ip wherein each Ra is H, pis 2, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d) aregiven in Table 1.

Table CLIII provides 782 compounds of formula Iq wherein each Ra is H, pis 2, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d) aregiven in Table 1.

Table CLIV provides 782 compounds of formula Ir wherein each Ra is H, pis 2, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d) aregiven in Table 1.

Table CLV provides 782 compounds of formula Is wherein each Ra is H, pis 2, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d) aregiven in Table 1.

Table CLVI provides 782 compounds of formula It wherein each Ra is H, pis 2, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d) aregiven in Table 1.

Table CLVII provides 782 compounds of formula Iu wherein each Ra is H, pis 2, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d) aregiven in Table 1.

Table CLVIII provides 782 compounds of formula Iv wherein each Ra is H,p is 2, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d)are given in Table 1.

Table CLIX provides 782 compounds of formula Iw wherein each Ra is H, pis 2, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d) aregiven in Table 1.

Table CLX provides 782 compounds of formula Ix wherein each Ra is H, pis 2, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d) aregiven in Table 1.

Table CLXI provides 782 compounds of formula Iy wherein each Ra is H, pis 2, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d) aregiven in Table 1.

Table CLXII provides 782 compounds of formula Iz wherein each Ra is H, pis 2, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d) aregiven in Table 1.

Table CLXIII provides 782 compounds of formula Iaa wherein each Ra is H,p is 2, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d)are given in Table 1.

Table CLXIV provides 782 compounds of formula Iab wherein each Ra is H,p is 2, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d)are given in Table 1.

Table CLXV provides 782 compounds of formula Iac wherein each Ra is H, pis 2, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d) aregiven in Table 1.

Table CLXVI provides 782 compounds of formula Iad wherein each Ra is H,p is 2, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d)are given in Table 1.

Table CLXVII provides 782 compounds of formula Iae wherein each Ra is H,p is 2, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d)are given in Table 1.

Table CLXIII provides 782 compounds of formula Iaf wherein each Ra is H,p is 2, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d)are given in Table 1.

Table CLXIX provides 782 compounds of formula Iag wherein each Ra is H,p is 2, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d)are given in Table 1.

Table CLXX provides 782 compounds of formula Iah wherein each Ra is H, pis 2, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d) aregiven in Table 1.

Table CLXXI provides 782 compounds of formula Iai wherein each Ra is H,p is 2, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d)are given in Table 1.

Table CLXXII provides 782 compounds of formula Iaj wherein each Ra is H,p is 2, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d)are given in Table 1.

Table CLXXIII provides 782 compounds of formula Iak wherein each Ra isH, p is 2, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) andR^(4d) are given in Table 1.

Table CLXXIV provides 782 compounds of formula Ial wherein each Ra is H,p is 2, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d)are given in Table 1.

Table CLXXV provides 782 compounds of formula Iam wherein each Ra is H,p is 2, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d)are given in Table 1.

Table CLXXVI provides 782 compounds of formula Ian wherein each Ra is H,p is 2, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d)are given in Table 1.

Table CLXXVII provides 782 compounds of formula Iao wherein each Ra isH, p is 2, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) andR^(4d) are given in Table 1.

Table CLXXVIII provides 782 compounds of formula Iap wherein each Ra isH, p is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d) aregiven in Table 1.

Table CLXXIX provides 782 compounds of formula Iaq wherein each Ra is H,p is 2, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d)are given in Table 1.

Table CLXXX provides 782 compounds of formula Iar wherein each Ra is H,p is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d) are givenin Table 1.

Table CLXXXI provides 782 compounds of formula Ias wherein each Ra is H,p is 2, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d)are given in Table 1.

Table CLXXXII provides 782 compounds of formula Iat wherein each Ra isH, p is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d) aregiven in Table 1.

Table CLXXXIII provides 782 compounds of formula Iau wherein each Ra isH, p is 2, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) andR^(4d) are given in Table 1.

Table CLXXXIV provides 782 compounds of formula Iav wherein each Ra isH, p is 2, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) andR^(4d) are given in Table 1.

Table CLXXXV provides 782 compounds of formula Iaw wherein each Ra is H,p is 2, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d)are given in Table 1.

Table CLXXXVI provides 782 compounds of formula Iax wherein each Ra isH, p is 2, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) andR^(4d) are given in Table 1.

Table CLXXXVII provides 782 compounds of formula Iay wherein each Ra isH, p is 2, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) andR^(4d) are given in Table 1.

Table CLXXXVIII provides 782 compounds of formula Iaz wherein each Ra isH, p is 2, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) andR^(4d) are given in Table 1.

Table CLXXXIX provides 782 compounds of formula % a wherein each Ra isH, p is 2, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) andR^(4d) are given in Table 1.

Table CXC provides 782 compounds of formula Ibb wherein each Ra is H, pis 2, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d) aregiven in Table 1.

Table CXCI provides 782 compounds of formula Ibc wherein each Ra is H, pis 2, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d) aregiven in Table 1.

Table CXCII provides 782 compounds of formula Ibd wherein each Ra is H,p is 2, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d)are given in Table 1.

Table CXCIII provides 782 compounds of formula Ibe wherein each Ra is H,p is 2, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d)are given in Table 1.

Table CXCIV provides 782 compounds of formula Ibf wherein each Ra is H,p is 2, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d)are given in Table 1.

Table CXCV provides 782 compounds of formula Ibg wherein each Ra is H, pis 2, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d) aregiven in Table 1.

Table CXCVI provides 782 compounds of formula Ibh wherein each Ra is H,p is 2, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d)are given in Table 1.

Table CXCVII provides 782 compounds of formula Ibi wherein each Ra is H,p is 2, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d)are given in Table 1.

Table CXCVIII provides 782 compounds of formula Ibj wherein each Ra isH, p is 2, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) andR^(4d) are given in Table 1.

Table CXCIX provides 782 compounds of formula Ibk wherein each Ra is H,p is 2, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d)are given in Table 1.

Table CC provides 782 compounds of formula Ibl wherein each Ra is H, pis 2, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d) aregiven in Table 1.

Table CCI provides 782 compounds of formula Ibm wherein each Ra is H, pis 2, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d) aregiven in Table 1.

Table CCII provides 782 compounds of formula Ibn wherein each Ra is H, pis 2, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d) aregiven in Table 1.

Table CCIII provides 782 compounds of formula Ibo wherein each Ra is H,p is 2, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d)are given in Table 1.

Table CCIV provides 782 compounds of formula Ibp wherein each Ra is H, pis 2, q is 3 and the values of R⁸, R^(4a), R^(4b), R^(4c) and R^(4d) aregiven in Table 1.

Mass spectra data were obtained for selected compounds of Tables ItoCCIV using LCMS: LC5: 254 nm−gradient 10% A to 100% B A=H2O+0.01% HCOOHB=CH₃CN/CH₃OH+0.01% HCOOH positive electrospray 150-1000 m/z.

The data are shown in Table 2.

Table 2

LCMS Compound (Ret. Time, min) MS data III-3 464/466 III-49 2′46498/500/502 LXXI-3 2′38 478/480 LXXI-26 2′49 496/498 CXXXIX-49 2′39526/528/530 CXLI-49 2′55 560/562/564

The compounds of the invention may be made by a variety of methods. Forexample they may be prepared according to the reactions of Scheme 1.

Thus a compound of formula 1 may be synthesised from compounds offormula 4 by reaction with an alkylating agent of the formula R⁸-L,where L is chloride, bromide, iodide or a sulfonate (e.g. mesylate ortosylate) or similar leaving group at a temperature of between ambienttemperature and 100° C., typically ambient temperature, in an organicsolvent such as acetonitrile, dimethylformamide, dichloromethane,chloroform or 1,2-dichloroethane in the presence of a tertiary aminebase such as triethylamine or diisopropylethylamine and optionallycatalysed by halide salts such as sodium iodide, potassium iodide ortetrabutylammonium iodide.

Alternatively, a compound of formula 4 may be reacted with an aldehydeof the formula RCHO at a temperature between ambient temperature and100° C. in an organic solvent such as tetrahydrofuran or ethanol ormixtures of solvents in the presence of a reducing agent such asborane-pyridine complex, sodium borohydride, sodium(triacetoxy)borohydride, sodium cyanoborohydride or such like, toproduce a compound of formula 1 where R8 is CH₂—R.

Compounds of formula 1 may also be obtained from compounds of formula 2bby reaction with a suitable electrophilic species. Compounds of formula1 where Y is a carbonyl group may be formed by the reaction of compoundsof formula 4 with a carboxylic acid derivative of formula R1-C(O)—Zwhere Z is chloride, hydroxy, alkoxy or acyloxy at a temperature between0° C. and 150° C. optionally in an organic solvent such asdichloromethane, chloroform or 1,2-dichloroethane, optionally in thepresence of a tertiary amine base such as triethylamine ordiisopropylethylamine and optionally in the presence of a coupling agentsuch as dicyclohexylcarbodiimide. Compounds of formula 1 where Y is acarbonyl group and R1 is an amino substituent of formula R′—NH— may beformed by the reaction of compounds of formula 2b with an isocyanate offormula R′—N═C═O under similar conditions. Compounds of formula 1 whereY is a group of formula S(O)_(q) may be formed from compounds of formula2b by treatment with compounds of formula of R1-S(O)_(q)—Cl undersimilar conditions. Compounds of formula 1 where Y is a thiocarbonylgroup and R1 is an amino substituent of formula R′—NH— may be formed bythe reaction of compounds of formula 2b with an isothiocyanate offormula R′—N═C═S under similar conditions.

Alternatively compounds of formula 1 where Y is a thiocarbonyl group andR1 is a carbon substituent may be formed by treatment of compounds offormula 1 where Y is a carbonyl group and R1 is a carbon substituentwith a suitable thionating agent such as Lawesson's reagent.

In the above procedures, acid derivatives of the formula R1-C(O)—Z,isocyanates of formula R′—N═C═O, isothiocyanates of formula R′—N═C═S andsulfur electrophiles of formula R1-S(O)_(q)—Cl are either knowncompounds or may be formed from known compounds by known methods by aperson skilled in the art.

A compound of formula 4 may be obtained from a compound of formula 3 byreaction with an acid such as trifluoroacetic acid at ambienttemperature in an organic solvent such as dichloromethane, chloroform or1,2-dichloroethane followed by neutralisation of the reaction mixturewith an aqueous solution of an inorganic base such as sodium carbonate,sodium bicarbonate or similar compound.

A compound of formula 3 may be obtained from a compound of formula 2a byreaction with a suitable electrophilic species, as described above.

Compounds of formula 2a and 2b may be synthesised as described in Scheme2. Thus, compounds of formula 2a may be obtained by reacting compoundsof formula 6a with compounds of formula 5 at a temperature of between 0°C. and 100° C. in an organic solvent such as dichloromethane, chloroformor 1,2-dichloroethane in the presence of an acid such as hydrochloricacid or trifluoroacetic acid and optionnally a co-solvent such as water,methanol or ethanol. The intermediates formed are subsequently treatedwith a reducing agent such as sodium borohydride, sodium(triacetoxy)borohydride, sodium cyanoborohydride, triethylsilane orsimilar at ambient temperature in organic solvent such as ethanol orchloroform or with a nucleophile R3-M (where M is a metallic species;R3-M is for example a Gringnard reagent).

Similarly, compounds of formula 2b may be synthesised by reactingcompounds of formula 6b with compounds of formula 5 using the conditionsdescribed above.

Compounds of formula 6a may be obtained from compounds of formula 7a byreaction with a 1-alkoxy substituted phosphonium salt such asmethoxymethyl(triphenyl)phosphonium chloride and a base such aspotassium tert-butoxide at a temperature of 0° C. to room temperature intetrahydrofuran.

Similarly, compounds of formula 6b may be synthesised from compounds offormula 7b using the conditions described above.

Compounds of formula 7a and 7b are either known compounds or may beformed from known compounds by known methods by a person skilled in theart.

A compound of formula 2a, in which p=1 and q=3 may be obtained as shownin Scheme 3.

Thus, a compound of formula 8 may be reduced to a compound of formula 2bin the presence of a reducing agent such as lithium aluminium,bis(2-methoxyethoxy)aluminium hydride or borane at a temperature ofbetween 0° C. and 120° C. in an organic solvent such as tetrahydrofuran,diethyl ether, benzene or toluene. A basic procedure is described inSynth. Commun. 1992, 22(5), 729-733.

Compounds of formula 8 may be synthesised by cyclising compounds offormula 9 under radical conditions such as tributyltin hydride in thepresence of a radical initiator such as1,1′-azobis(cyclohexanecarbonitrile) in an organic solvent such asbenzene or toluene at a temperature of between 60 C and 120° C.,followed by removal of the acetyl protecting group using a base such assodium hydroxide or potassium hydroxide in an organic solvent such asmethanol, ethanol or water at a temperature of between 0° C. to 100° C.

Compounds of formula 9 may be synthesised by acylating compounds offormula 11 using known methods by the person skilled in the art.

Alternatively a compound of formula 8 may be obtained by hydrogenationof a compound of formula 10, which may be obtained from a compound offormula 11 by cyclising a compound of formula 10 under Heck conditionsin the presence of a catalyst such as palladium(II) acetate, optionallya ligand such as triphenylphosphine or/and an additive such astetrabutylammonium bromide and a base such as triethylamine in anorganic solvent such as tetrahydrofuran, acetonitrile ordimethylformamide at a temperature of between 50° C. to 140° C. A basicprocedure is described in WO 01/05790.

Compounds of formula 11 may be synthesised by reacting the knowncompound of formula 12 (Chem. Commun. 1999, 1757-1758) with compounds offormula 13 at temperatures of between 0° C. to 60° C. in an organicsolvent such as dichloromethane, benzene or toluene in the presence of atrialkylaluminium reagent such as trimethylaluminium.

Compounds of formula 13 are either known compounds or may be formed fromknown compounds by known methods by a person skilled in the art.

Alternatively a compound of formula 2b, in which p=1 and q=2 may beobtained as shown in Scheme 4.

Thus, compounds of formula 14 may react with a reducing agent such asbis(2-methoxyethoxy)aluminium hydride at a temperature of between 0° C.and 120° C. in an organic solvent such as benzene or toluene to providecompounds of formula 2b, in which p=1 and q=2.

Compounds of formula 14 may be synthesised from compounds of formula 15by reaction with an alkylating agent of the formula R8-L, where L ischloride, bromide, iodide or a sulfonate (e.g. mesylate or tosylate) orsimilar leaving group, as described above.

Compounds of formula 15 may be obtained by radical cyclisation ofcompounds of formula 16 using the method described in Org. Lett. 2000,23, 3599-3601.

Compounds of formula 16 may be synthesised by coupling compounds offormula 18 with the known alcohol 19 (J. Org. Chem. 2001, 66, 5545-5551)under Mitsunobu conditions.

Compounds of formula 18 are either known compounds or may be formed fromknown compounds such as 20 by known methods by a person skilled in theart.

Certain compounds of formula 2a, 2b, 3, 4 and 10 are novel and as suchform a further aspect of the invention.

The compounds of formula (I) can be used to combat and controlinfestations of insect pests such as Lepidoptera, Diptera, Hemiptera,Thysanoptera, Orthoptera, Dictyoptera, Coleoptera, Siphonaptera,Hymenoptera and Isoptera and also other invertebrate pests, for example,acarine, nematode and mollusc pests. Insects, acarines, nematodes andmolluscs are hereinafter collectively referred to as pests. The pestswhich may be combated and controlled by the use of the inventioncompounds include those pests associated with agriculture (which termincludes the growing of crops for food and fibre products), horticultureand animal husbandry, companion animals, forestry and the storage ofproducts of vegetable origin (such as fruit, grain and timber); thosepests associated with the damage of man-made structures and thetransmission of diseases of man and animals; and also nuisance pests(such as flies).

Examples of pest species which may be controlled by the compounds offormula (I) include: Myzus persicae (aphid), Aphis gossypii (aphid),Aphis fabae (aphid), Lygus spp. (capsids), Dysdercus spp. (capsids),Nilaparvata lugens (planthopper), Nephotettixc incticeps (leafhopper),Nezara spp. (stinkbugs), Euschistus spp. (stinkbugs), Leptocorisa spp.(stinkbugs), Frankliniella occidentalis (thrip), Thrips spp. (thrips),Leptinotarsa decemlineata (Colorado potato beetle), Anthonomus grandis(boll weevil), Aonidiella spp. (scale insects), Trialeurodes spp. (whiteflies), Bemisia tabaci (white fly), Ostrinia nubilalis (European cornborer), Spodoptera littoralis (cotton leafworm), Heliothis virescens(tobacco budworm), Helicoverpa armigera (cotton bollworm), Helicoverpazea (cotton bollworm), Sylepta derogata (cotton leaf roller), Pierisbrassicae (white butterfly), Plutella xylostella (diamond back moth),Agrotis spp. (cutworms), Chilo suppressalis (rice stem borer), Locustamigratoria (locust), Chortiocetes terminifera (locust), Diabrotica spp.(rootworms), Panonychus ulmi (European red mite), Panonychus citri(citrus red mite), Tetranychus urticae (two-spotted spider mite),Tetranychus cinnabarinus (carmine spider mite), Phyllocoptruta oleivora(citrus rust mite), Polyphagotarsonemus latus (broad mite), Brevipalpusspp. (flat mites), Boophilus microplus (cattle tick), Dermacentorvariabilis (American dog tick), Ctenocephalides fells (cat flea),Liriomyza spp. (leafminer), Musca domestica (housefly), Aedes aegypti(mosquito), Anopheles spp. (mosquitoes), Culex spp. (mosquitoes),Lucillia spp. (blowflies), Blattella germanica (cockroach), Periplanetaamericana (cockroach), Blatta orientalis (cockroach), termites of theMastotermitidae (for example Mastotermes spp.), the Kalotermitidae (forexample Neotermes spp.), the Rhinotermitidae (for example Coptotermesformosanus, Reticulitermes flavipes, R. speratu, R. virginicus, R.hesperus, and R. santonensis) and the Termitidae (for exampleGlobitermes sulphureus), Solenopsis geminata (fire ant), Monomoriumpharaonis (pharaoh's ant), Damalinia spp. and Linognathus spp. (bitingand sucking lice), Meloidogyne spp. (root knot nematodes), Globoderaspp. and Heterodera spp. (cyst nematodes), Pratylenchus spp. (lesionnematodes), Rhodopholus spp. (banana burrowing nematodes), Tylenchulusspp. (citrus nematodes), Haemonchus contortus (barber pole worm),Caenorhabditis elegans (vinegar eelworm), Trichostrongylus spp. (gastrointestinal nematodes) and Deroceras reticulatum (slug).

The invention therefore provides a method of combating and controllinginsects, acarines, nematodes or molluscs which comprises applying aninsecticidally, acaricidally, nematicidally or molluscicidally effectiveamount of a compound of formula (I), or a composition containing acompound of formula (I), to a pest, a locus of pest, or to a plantsusceptible to attack by a pest, The compounds of formula (I) arepreferably used against insects, acarines or nematodes.

The term “plant” as used herein includes seedlings, bushes and trees.

In order to apply a compound of formula (I) as an insecticide,acaricide, nematicide or molluscicide to a pest, a locus of pest, or toa plant susceptible to attack by a pest, a compound of formula (I) isusually formulated into a composition which includes, in addition to thecompound of formula (I), a suitable inert diluent or carrier and,optionally, a surface active agent (SFA). SFAs are chemicals which areable to modify the properties of an interface (for example,liquid/solid, liquid/air or liquid/liquid interfaces) by lowering theinterfacial tension and thereby leading to changes in other properties(for example dispersion, emulsification and wetting). It is preferredthat all compositions (both solid and liquid formulations) comprise, byweight, 0.0001 to 95%, more preferably 1 to 85%, for example 5 to 60%,of a compound of formula (I). The composition is generally used for thecontrol of pests such that a compound of formula (I) is applied at arate of from 0.1 g to 10 kg per hectare, preferably from 1 g to 6 kg perhectare, more preferably from 1 g to 1 kg per hectare.

When used in a seed dressing, a compound of formula (I) is used at arate of 0.0001 g to 10 g (for example 0.001 g or 0.05 g), preferably0.005 g to 10 g, more preferably 0.005 g to 4 g, per kilogram of seed.

In another aspect the present invention provides an insecticidal,acaricidal, nematicidal or molluscicidal composition comprising aninsecticidally, acaricidally, nematicidally or molluscicidally effectiveamount of a compound of formula (I) and a suitable carrier or diluenttherefor. The composition is preferably an insecticidal, acaricidal,nematicidal or molluscicidal composition.

In a still further aspect the invention provides a method of combatingand controlling pests at a locus which comprises treating the pests orthe locus of the pests with an insecticidally, acaricidally,nematicidally or molluscicidally effective amount of a compositioncomprising a compound of formula (I). The compounds of formula (I) arepreferably used against insects, acarines or nematodes.

The compositions can be chosen from a number of formulation types,including dustable powders (DP), soluble powders (SP), water solublegranules (SG), water dispersible granules (WG), wettable powders (WP),granules (GR) (slow or fast release), soluble concentrates (SL), oilmiscible liquids (OL), ultra low volume liquids (UL), emulsifiableconcentrates (EC), dispersible concentrates (DC), emulsions (both oil inwater (EW) and water in oil (EO)), micro-emulsions (ME), suspensionconcentrates (SC), aerosols, fogging/smoke formulations, capsulesuspensions (CS) and seed treatment formulations. The formulation typechosen in any instance will depend upon the particular purpose envisagedand the physical, chemical and biological properties of the compound offormula (I).

Dustable powders (DP) may be prepared by mixing a compound of formula(I) with one or more solid diluents (for example natural clays, kaolin,pyrophyllite, bentonite, alumina, montmorillonite, kieselguhr, chalk,diatomaceous earths, calcium phosphates, calcium and magnesiumcarbonates, sulphur, lime, flours, talc and other organic and inorganicsolid carriers) and mechanically grinding the mixture to a fine powder.

Soluble powders (SP) may be prepared by mixing a compound of formula (I)with one or more water-soluble inorganic salts (such as sodiumbicarbonate, sodium carbonate or magnesium sulphate) or one or morewater-soluble organic solids (such as a polysaccharide) and, optionally,one or more wetting agents, one or more dispersing agents or a mixtureof said agents to improve water dispersibility/solubility. The mixtureis then ground to a fine powder. Similar compositions may also begranulated to form water soluble granules (SG).

Wettable powders (WP) may be prepared by mixing a compound of formula(I) with one or more solid diluents or carriers, one or more wettingagents and, preferably, one or more dispersing agents and, optionally,one or more suspending agents to facilitate the dispersion in liquids.The mixture is then ground to a fine powder. Similar compositions mayalso be granulated to form water dispersible granules (WG).

Granules (GR) may be formed either by granulating a mixture of acompound of formula (I) and one or more powdered solid diluents orcarriers, or from pre-formed blank granules by absorbing a compound offormula (I) (or a solution thereof, in a suitable agent) in a porousgranular material (such as pumice, attapulgite clays, fuller's earth,kieselguhr, diatomaceous earths or ground corn cobs) or by adsorbing acompound of formula (I) (or a solution thereof, in a suitable agent) onto a hard core material (such as sands, silicates, mineral carbonates,sulphates or phosphates) and drying if necessary. Agents which arecommonly used to aid absorption or adsorption include solvents (such asaliphatic and aromatic petroleum solvents, alcohols, ethers, ketones andesters) and sticking agents (such as polyvinyl acetates, polyvinylalcohols, dextrins, sugars and vegetable oils). One or more otheradditives may also be included in granules (for example an emulsifyingagent, wetting agent or dispersing agent).

Dispersible Concentrates (DC) may be prepared by dissolving a compoundof formula (I) in water or an organic solvent, such as a ketone, alcoholor glycol ether. These solutions may contain a surface active agent (forexample to improve water dilution or prevent crystallisation in a spraytank).

Emulsifiable concentrates (EC) or oil-in-water emulsions (EW) may beprepared by dissolving a compound of formula (I) in an organic solvent(optionally containing one or more wetting agents, one or moreemulsifying agents or a mixture of said agents). Suitable organicsolvents for use in ECs include aromatic hydrocarbons (such asalkylbenzenes or alkylnaphthalenes, exemplified by SOLVESSO 100,SOLVESSO 150 and SOLVESSO 200; SOLVESSO is a Registered Trade Mark),ketones (such as cyclohexanone or methylcyclohexanone) and alcohols(such as benzyl alcohol, furfuryl alcohol or butanol),N-alkylpyrrolidones (such as N-methylpyrrolidone or N-octylpyrrolidone),dimethyl amides of fatty acids (such as C₈-C₁₀ fatty acid dimethylamide)and chlorinated hydrocarbons. An EC product may spontaneously emulsifyon addition to water, to produce an emulsion with sufficient stabilityto allow spray application through appropriate equipment. Preparation ofan EW involves obtaining a compound of formula (I) either as a liquid(if it is not a liquid at room temperature, it may be melted at areasonable temperature, typically below 70° C.) or in solution (bydissolving it in an appropriate solvent) and then emulsifiying theresultant liquid or solution into water containing one or more SFAs,under high shear, to produce an emulsion. Suitable solvents for use inEWs include vegetable oils, chlorinated hydrocarbons (such aschlorobenzenes), aromatic solvents (such as alkylbenzenes oralkylnaphthalenes) and other appropriate organic solvents which have alow solubility in water.

Microemulsions (ME) may be prepared by mixing water with a blend of oneor more solvents with one or more SFAs, to produce spontaneously athermodynamically stable isotropic liquid formulation. A compound offormula (I) is present initially in either the water or the solvent/SFAblend. Suitable solvents for use in MEs include those hereinbeforedescribed for use in in ECs or in EWs. An ME may be either anoil-in-water or a water-in-oil system (which system is present may bedetermined by conductivity measurements) and may be suitable for mixingwater-soluble and oil-soluble pesticides in the same formulation. An MEis suitable for dilution into water, either remaining as a microemulsionor forming a conventional oil-in-water emulsion.

Suspension concentrates (SC) may comprise aqueous or non-aqueoussuspensions of finely divided insoluble solid particles of a compound offormula (I). SCs may be prepared by ball or bead milling the solidcompound of formula (I) in a suitable medium, optionally with one ormore dispersing agents, to produce a fine particle suspension of thecompound. One or more wetting agents may be included in the compositionand a suspending agent may be included to reduce the rate at which theparticles settle. Alternatively, a compound of formula (I) may be drymilled and added to water, containing agents hereinbefore described, toproduce the desired end product.

Aerosol formulations comprise a compound of formula (I) and a suitablepropellant (for example n-butane). A compound of formula (I) may also bedissolved or dispersed in a suitable medium (for example water or awater miscible liquid, such as n-propanol) to provide compositions foruse in non-pressurised, hand-actuated spray pumps.

A compound of formula (I) may be mixed in the dry state with apyrotechnic mixture to form a composition suitable for generating, in anenclosed space, a smoke containing the compound.

Capsule suspensions (CS) may be prepared in a manner similar to thepreparation of EW formulations but with an additional polymerisationstage such that an aqueous dispersion of oil droplets is obtained, inwhich each oil droplet is encapsulated by a polymeric shell and containsa compound of formula (I) and, optionally, a carrier or diluenttherefor. The polymeric shell may be produced by either an interfacialpolycondensation reaction or by a coacervation procedure. Thecompositions may provide for controlled release of the compound offormula (I) and they may be used for seed treatment. A compound offormula (I) may also be formulated in a biodegradable polymeric matrixto provide a slow, controlled release of the compound.

A composition may include one or more additives to improve thebiological performance of the composition (for example by improvingwetting, retention or distribution on surfaces; resistance to rain ontreated surfaces; or uptake or mobility of a compound of formula (I)).Such additives include surface active agents, spray additives based onoils, for example certain mineral oils or natural plant oils (such assoy bean and rape seed oil), and blends of these with otherbio-enhancing adjuvants (ingredients which may aid or modify the actionof a compound of formula (I)).

A compound of formula (I) may also be formulated for use as a seedtreatment, for example as a powder composition, including a powder fordry seed treatment (DS), a water soluble powder (SS) or a waterdispersible powder for slurry treatment (WS), or as a liquidcomposition, including a flowable concentrate (FS), a solution (LS) or acapsule suspension (CS). The preparations of DS, SS, WS, FS and LScompositions are very similar to those of, respectively, DP, SP, WP, SCand DC compositions described above. Compositions for treating seed mayinclude an agent for assisting the adhesion of the composition to theseed (for example a mineral oil or a film-forming barrier).

Wetting agents, dispersing agents and emulsifying agents may be surfaceSFAs of the cationic, anionic, amphoteric or non-ionic type.

Suitable SFAs of the cationic type include quaternary ammonium compounds(for example cetyltrimethyl ammonium bromide), imidazolines and aminesalts.

Suitable anionic SFAs include alkali metals salts of fatty acids, saltsof aliphatic monoesters of sulphuric acid (for example sodium laurylsulphate), salts of sulphonated aromatic compounds (for example sodiumdodecylbenzenesulphonate, calcium dodecylbenzenesulphonate,butylnaphthalene sulphonate and mixtures of sodium di-isopropyl- andtri-isopropyl-naphthalene sulphonates), ether sulphates, alcohol ethersulphates (for example sodium laureth-3-sulphate), ether carboxylates(for example sodium laureth-3-carboxylate), phosphate esters (productsfrom the reaction between one or more fatty alcohols and phosphoric acid(predominately mono-esters) or phosphorus pentoxide (predominatelydi-esters), for example the reaction between lauryl alcohol andtetraphosphoric acid; additionally these products may be ethoxylated),sulphosuccinamates, paraffin or olefine sulphonates, taurates andlignosulphonates.

Suitable SFAs of the amphoteric type include betaines, propionates andglycinates.

Suitable SFAs of the non-ionic type include condensation products ofalkylene oxides, such as ethylene oxide, propylene oxide, butylene oxideor mixtures thereof, with fatty alcohols (such as oleyl alcohol or cetylalcohol) or with alkylphenols (such as octylphenol, nonylphenol oroctylcresol); partial esters derived from long chain fatty acids orhexitol anhydrides; condensation products of said partial esters withethylene oxide; block polymers (comprising ethylene oxide and propyleneoxide); alkanolamides; simple esters (for example fatty acidpolyethylene glycol esters); amine oxides (for example lauryl dimethylamine oxide); and lecithins.

Suitable suspending agents include hydrophilic colloids (such aspolysaccharides, polyvinylpyrrolidone or sodium carboxymethylcellulose)and swelling clays (such as bentonite or attapulgite).

A compound of formula (I) may be applied by any of the known means ofapplying pesticidal compounds. For example, it may be applied,formulated or unformulated, to the pests or to a locus of the pests(such as a habitat of the pests, or a growing plant liable toinfestation by the pests) or to any part of the plant, including thefoliage, stems, branches or roots, to the seed before it is planted orto other media in which plants are growing or are to be planted (such assoil surrounding the roots, the soil generally, paddy water orhydroponic culture systems), directly or it may be sprayed on, dustedon, applied by dipping, applied as a cream or paste formulation, appliedas a vapour or applied through distribution or incorporation of acomposition (such as a granular composition or a composition packed in awater-soluble bag) in soil or an aqueous environment.

A compound of formula (I) may also be injected into plants or sprayedonto vegetation using electrodynamic spraying techniques or other lowvolume methods, or applied by land or aerial irrigation systems.

Compositions for use as aqueous preparations (aqueous solutions ordispersions) are generally supplied in the form of a concentratecontaining a high proportion of the active ingredient, the concentratebeing added to water before use. These concentrates, which may includeDCs, SCs, ECs, EWs, MEs SGs, SPs, WPs, WGs and CSs, are often requiredto withstand storage for prolonged periods and, after such storage, tobe capable of addition to water to form aqueous preparations whichremain homogeneous for a sufficient time to enable them to be applied byconventional spray equipment. Such aqueous preparations may containvarying amounts of a compound of formula (I) (for example 0.0001 to 10%,by weight) depending upon the purpose for which they are to be used.

A compound of formula (I) may be used in mixtures with fertilisers (forexample nitrogen-, potassium- or phosphorus-containing fertilisers).Suitable formulation types include granules of fertiliser. The mixturessuitably contain up to 25% by weight of the compound of formula (I).

The invention therefore also provides a fertiliser compositioncomprising a fertiliser and a compound of formula (I).

The compositions of this invention may contain other compounds havingbiological activity, for example micronutrients or compounds havingfungicidal activity or which possess plant growth regulating,herbicidal, insecticidal, nematicidal or acaricidal activity.

The compound of formula (I) may be the sole active ingredient of thecomposition or it may be admixed with one or more additional activeingredients such as a pesticide, fungicide, synergist, herbicide orplant growth regulator where appropriate. An additional activeingredient may: provide a composition having a broader spectrum ofactivity or increased persistence at a locus; synergise the activity orcomplement the activity (for example by increasing the speed of effector overcoming repellency) of the compound of formula (I); or help toovercome or prevent the development of resistance to individualcomponents. The particular additional active ingredient will depend uponthe intended utility of the composition. Examples of suitable pesticidesinclude the following: a) Pyrethroids, such as permethrin, cypermethrin,fenvalerate, esfenvalerate, deltamethrin, cyhalothrin (in particularlambda-cyhalothrin), bifenthrin, fenpropathrin, cyfluthrin, tefluthrin,fish safe pyrethroids (for example ethofenprox), natural pyrethrin,tetramethrin, s-bioallethrin, fenfluthrin, prallethrin or5-benzyl-3-furylmethyl-(E)-(1R,3S)-2,2-dimethyl-3-(2-oxothiolan-3-ylidenemethyl)cyclopropanecarboxylate;

b) Organophosphates, such as, profenofos, sulprofos, acephate, methylparathion, azinphos-methyl, demeton-s-methyl, heptenophos, thiometon,fenamiphos, monocrotophos, profenofos, triazophos, methamidophos,dimethoate, phosphamidon, malathion, chlorpyrifos, phosalone, terbufos,fensulfothion, fonofos, phorate, phoxim, pirimiphos-methyl,pirimiphos-ethyl, fenitrothion, fosthiazate or diazinon;c) Carbamates (including aryl carbamates), such as pirimicarb,triazamate, cloethocarb, carbofuran, furathiocarb, ethiofencarb,aldicarb, thiofurox, carbosulfan, bendiocarb, fenobucarb, propoxur,methomyl or oxamyl;d) Benzoyl ureas, such as diflubenzuron, triflumuron, hexaflumuron,flufenoxuron or chlorfluazuron;e) Organic tin compounds, such as cyhexatin, fenbutatin oxide orazocyclotin;f) Pyrazoles, such as tebufenpyrad and fenpyroximate;g) Macrolides, such as avermectins or milbemycins, for exampleabamectin, emamectin benzoate, ivermectin, milbemycin, spinosad orazadirachtin;h) Hormones or pheromones;i) Organochlorine compounds such as endosulfan, benzene hexachloride,DDT, chlordane or dieldrin;j) Amidines, such as chlordimeform or amitraz;k) Fumigant agents, such as chloropicrin, dichloropropane, methylbromide or metam;l) Chloronicotinyl compounds such as imidacloprid, thiacloprid,acetamiprid, nitenpyram or thiamethoxam;m) Diacylhydrazines, such as tebufenozide, chromafenozide ormethoxyfenozide;n) Diphenyl ethers, such as diofenolan or pyriproxifen;

o) Indoxacarb; p) Chlorfenapyr; or q) Pymetrozine.

In addition to the major chemical classes of pesticide listed above,other pesticides having particular targets may be employed in thecomposition, if appropriate for the intended utility of the composition.For instance, selective insecticides for particular crops, for examplestemborer specific insecticides (such as cartap) or hopper specificinsecticides (such as buprofezin) for use in rice may be employed.Alternatively insecticides or acaricides specific for particular insectspecies/stages may also be included in the compositions (for exampleacaricidal ovo-larvicides, such as clofentezine, flubenzimine,hexythiazox or tetradifon; acaricidal motilicides, such as dicofol orpropargite; acaricides, such as bromopropylate or chlorobenzilate; orgrowth regulators, such as hydramethylnon, cyromazine, methoprene,chlorfluazuron or diflubenzuron).

Examples of fungicidal compounds which may be included in thecomposition of the invention are(E)-N-methyl-2-[2-(2,5-dimethylphenoxymethyl)phenyl]-2-methoxy-iminoacetamide(SSF-129),4-bromo-2-cyano-N,N-dimethyl-6-trifluoromethyl-benzimidazole-1-sulphonamide,α-[N-(3-chloro-2,6-xylyl)-2-methoxy-acetamido]-γ-butyrolactone,4-chloro-2-cyano-N,N-dimethyl-5-p-tolylimidazole-1-sulfonamide (IKF-916,cyamidazosulfamid),3-5-dichloro-N-(3-chloro-1-ethyl-1-methyl-2-oxopropyl)-4-methylbenzamide(RH-7281, zoxamide),N-allyl-4,5,-dimethyl-2-trimethylsilylthiophene-3-carboxamide(MON65500),N-(1-cyano-1,2-dimethylpropyl)-2-(2,4-dichlorophenoxy)propionamide(AC382042), N-(2-methoxy-5-pyridyl)-cyclopropane carboxamide,acibenzolar (CGA245704), alanycarb, aldimorph, anilazine, azaconazole,azoxystrobin, benalaxyl, benomyl, biloxazol, bitertanol, blasticidin S,bromuconazole, bupirimate, captafol, captan, carbendazim, carbendazimchlorhydrate, carboxin, carpropamid, carvone, CGA41396, CGA41397,chinomethionate, chlorothalonil, chlorozolinate, clozylacon, coppercontaining compounds such as copper oxychloride, copper oxyquinolate,copper sulphate, copper tallate and Bordeaux mixture, cymoxanil,cyproconazole, cyprodinil, debacarb, di-2-pyridyl disulphide1,1′-dioxide, dichlofluanid, diclomezine, dicloran, diethofencarb,difenoconazole, difenzoquat, diflumetorim, O,O-di-iso-propyl-5-benzylthiophosphate, dimefluazole, dimetconazole, dimethomorph, dimethirimol,diniconazole, dinocap, dithianon, dodecyl dimethyl ammonium chloride,dodemorph, dodine, doguadine, edifenphos, epoxiconazole, ethirimol,ethyl(Z)—N-benzyl-N([methyl(methyl-thioethylideneaminooxycarbonyl)amino]thio)-β-alaninate,etridiazole, famoxadone, fenamidone (RPA407213), fenarimol,fenbuconazole, fenfuram, fenhexamid (KBR2738), fenpiclonil, fenpropidin,fenpropimorph, fentin acetate, fentin hydroxide, ferbam, ferimzone,fluazinam, fludioxonil, flumetover, fluoroimide, fluquinconazole,flusilazole, flutolanil, flutriafol, folpet, fuberidazole, furalaxyl,furametpyr, guazatine, hexaconazole, hydroxyisoxazole, hymexazole,imazalil, imibenconazole, iminoctadine, iminoctadine triacetate,ipconazole, iprobenfos, iprodione, iprovalicarb (SZX0722), isopropanylbutyl carbamate, isoprothiolane, kasugamycin, kresoxim-methyl, LY186054,LY211795, LY248908, mancozeb, maneb, mefenoxam, mepanipyrim, mepronil,metalaxyl, metconazole, metiram, metiram-zinc, metominostrobin,myclobutanil, neoasozin, nickel dimethyldithiocarbamate,nitrothal-isopropyl, nuarimol, ofurace, organomercury compounds,oxadixyl, oxasulfuron, oxolinic acid, oxpoconazole, oxycarboxin,pefurazoate, penconazole, pencycuron, phenazin oxide, phosetyl-Al,phosphorus acids, phthalide, picoxystrobin (ZA1963), polyoxin D,polyram, probenazole, prochloraz, procymidone, propamocarb,propiconazole, propineb, propionic acid, pyrazophos, pyrifenox,pyrimethanil, pyroquilon, pyroxyfur, pyrroInitrin, quaternary ammoniumcompounds, quinomethionate, quinoxyfen, quintozene, sipconazole (F-155),sodium pentachlorophenate, spiroxamine, streptomycin, sulphur,tebuconazole, tecloftalam, tecnazene, tetraconazole, thiabendazole,thifluzamid, 2-(thiocyanomethylthio)benzothiazole, thiophanate-methyl,thiram, timibenconazole, tolclofos-methyl, tolylfluanid, triadimefon,triadimenol, triazbutil, triazoxide, tricyclazole, tridemorph,trifloxystrobin (CGA279202), triforine, triflumizole, triticonazole,validamycin A, vapam, vinclozolin, zineb and ziram.

The compounds of formula (I) may be mixed with soil, peat or otherrooting media for the protection of plants against seed-borne,soil-borne or foliar fungal diseases.

Examples of suitable synergists for use in the compositions includepiperonyl butoxide, sesamex, safroxan and dodecyl imidazole.

Suitable herbicides and plant-growth regulators for inclusion in thecompositions will depend upon the intended target and the effectrequired.

An example of a rice selective herbicide which may be included ispropanil. An example of a plant growth regulator for use in cotton isPIX™.

Some mixtures may comprise active ingredients which have significantlydifferent physical, chemical or biological properties such that they donot easily lend themselves to the same conventional formulation type. Inthese circumstances other formulation types may be prepared. Forexample, where one active ingredient is a water insoluble solid and theother a water insoluble liquid, it may nevertheless be possible todisperse each active ingredient in the same continuous aqueous phase bydispersing the solid active ingredient as a suspension (using apreparation analogous to that of an SC) but dispersing the liquid activeingredient as an emulsion (using a preparation analogous to that of anEW). The resultant composition is a suspoemulsion (SE) formulation.

The invention is illustrated by the following Examples:

EXAMPLE 1

This Example illustrates the preparation of compound CXXXIX-49,5-chloro-1-(2-chloropyridin-4-yl)carbonyl-1′-[trans-3-(4-chlorophenyl)allyl]spiro[perhydro-azepine-3,3′-piperidine]

Step A: 4-Perhydroazepinone hydrochloride (2.5 g, prepared according toSynth. Commun. 1992, 1249-1258) was suspended in acetonitrile (80 ml);diisopropylethylamine (4.4 ml) and 4-chlorocinnamyl chloride (2.7 g)were successively added at room temperature and the resulting reactionmixture was stirred at room temperature for 20 hours. The solvent wasremoved in vacuo and the residue purified by silica gel chromatography(eluent cyclohexane:ethyl acetate 6:4) to afford1-(trans-3-(4-chlorophenyl)allyl)-perhydroazepin-4-one (1.84 g) as afoam. MS (ES+) 264/266 (M+H⁺).

Step B: To a stirred suspension of methoxymethyltriphenylphosphoniumchloride (3.9 g) in tetrahydrofuran (30 ml) at 0° C. unter argon wasadded portionwise potassium tert-butoxide (1.3 g) over 30 min.1-(trans-3-(4-chlorophenyl)allyl)-perhydroazepin-4-one (1.5 g) dissolvedin a minimum volume of tetrahydrofuran was added to the resulting orangesolution and the resulting mixture was stirred at room temperature for 2hours, quenched by addition of water, extracted twice with ethylacetate, the organic layers were dried (sodium sulphate) andconcentrated in vacuo. Silica gel chromatography (eluentcyclohexane:ethyl acetate 7:3) of the residue afforded1-[(E)-3-(4-Chloro-phenyl)-allyl]-4-[1-methoxy-meth-(Z)-ylidene]-perhydro-azepine(1.1 g) as an oil (1:1 mixture of isomers). MS (ES+) 292/296 (M+H⁺).

Step C: A mixture of-[(E)-3-(4-Chloro-phenyl)-allyl]-4-[1-methoxy-meth-(Z)-ylidene]-perhydro-azepine(0.6 g) and 4-chlorophenylhydrazine hydrochloride (0.41 g) in chloroform(20 ml) was treated with trifluoroacetic acid (2.1 ml) and heated atreflux under argon for 18 hours. The reaction mixture was cooled to roomtemperature, triethylsilane (3.1 ml) was added and the solution refluxedfor 2 hours. The reaction mixture was cooled to room temperature,diluted with dichloromethane, neutralised with 30% aqueous ammoniumhydroxide, washed with brine, dried (sodium sulphate) and concentrated.The dark residue was purified by silica gel chromatography(cyclohexane:ethyl acetate 1:9) to afford5-chloro-1′-[trans-3-(4-chlorophenyl)allyl]spiro[perhydro-azepine-3,3′-piperidine](529 mg). MS (ES+) 387/389 (M+H′).

Step D: To a solution of5-chloro-1′-[trans-3-(4-chlorophenyl)allyl]spiro[perhydro-azepine-3,3′-piperidine]obtained in Step C (250 mg) and triethylamine (0.42 ml) indichloromethane (10 ml) at 0° C. was added 2-chloro-isonicotinoylchloride (220 mg) and the resulting solution was kept at roomtemperature for 18 hours, diluted with dichloromethane, washed withdiluted aqueous sodium bicarbonate, dried (sodium sulphate) andconcentrated. Silica gel chromatography of the residue(cyclohexane:ethyl acetate 3:7) afforded the title compound as a yellowsolid (181 mg); M.p. 86-90° C.; MS (ES+) 526/528/530 (M+H⁺)

Compound CXLI-49 (M.p. 166-170° C.) was prepared according to proceduresanalogous to those described in Example 1.

EXAMPLE 2

This Example illustrates the preparation of compoundLXXI-3,1-(2-chloropyridin-4-yl)carbonyl-1′-[trans-3-(4-chlorophenyl)allyl]spiro[indoline-3,3′-piperidine]

Step A: Trimethylaluminium (2M in heptane, 3 ml) was added dropwise to asolution of 2-bromoaniline (860 mg) in dichloromethane (15 ml). Aftergas evolution ceased, 5,6-dihydro-2H-pyridine-1,3-dicarboxylic acid1-tert-butyl ester 3-methyl ester (Chem. Commun. 1999, 1757-1758, 1.2 g)dissolved in dichloromethane (10 ml) was added and the resulting mixturewas refluxed for 5 hrs. The solution was cooled to 0° C., quenched bycareful addition of saturated aqueous sodium bicarbonate (10 ml) andextracted with dichloromethane. The organic layer was washed with brine,dried (Na₂SO₄) and concentrated in vacuo. The residue was purified bysilica gel chromatography (eluent cyclohexane:ethyl acetate 85:15) toafford 5-(2-bromo-phenylcarbamoyl)-3,6-dihydro-2H-pyridine-1-carboxylicacid tert-butyl ester (1.2 g), which was characterised by its mass andNMR spectra.

Step B: To a stirred solution of the compound obtained in Step A (3.24g) in dimethylformamide (60 ml) under argon were added successivelytriethylamine (3 ml), tetrabutyammonium bromide (3.2 g) andpalladium(II) acetate (386 mg) and the resulting mixture was heatedunder reflux for 5 hours, cooled to room temperature, poured into brineand extracted with ethyl acetate. The organic layer was washed with HCl1N then water, dried over sodium sulfate and concentrated in vacuo. Theresidue was purified by silica gel chromatography (eluentcyclohexane:ethyl acetate 8:2) to affordspiro[indolin-2-one-3,3′-(1′,2′,3′,4′-tetrahydropyridine]-1′-carboxylicacid tert-butyl ester (1.2 g), which was characterised by its mass andNMR spectra.

Step C: Spiro[indolin-2-one-3,3′-piperidine]-1′-carboxylic acidtert-butyl ester obtained in Step B (1.12 g) was hydrogenated (1 atm.)in 15 ml tetrahydrofuran in the presence of 10% Pd/C (0.6 g) to affordafter standard work-upspiro[indolin-2-one-3,3′-piperidine]-1′-carboxylic acid tert-butyl ester(1.06 g), which was characterised by its mass and NMR spectra. MS (ES+)203 (M—CO₂-isoprene+H⁺), 247 (M-isoprene+H⁺), 303 (M+H⁺).

Step D: A solution of spiro[indolin-2-one-3,3′-piperidine]-1′-carboxylicacid tert-butyl ester obtained in Step C (650 mg) in toluene (20 ml) at70° C. under argon was treated with sodium bis(2-methoxyethoxy)aluminiumhydride (Red-Al, 65% in toluene, 1.3 ml) and the reaction mixture wasstirred at 75° C. for 2 hours, cooled to room temperature, quenched byaddition of ethyl acetate (20 ml), stirred for 15 min. and concentratedin vacuo. The residue was diluted with ethyl acetate, washed with waterand brine, dried over sodium sulfate and concentrated in vacuo. Theresidue was purified by silica gel chromatography (eluentcyclohexane:ethyl acetate 7:3) to affordspiro[indoline-3,3′-piperidine]-1′-carboxylic acid tert-butyl ester (331mg) as a colorless oil, which was characterised by its mass and NMRspectra. MS (ES+) 233 (M-isoprene+H⁺), 289 (M+H').

Step E: To a solution of spiro[indoline-3,3′-piperidine]-1′-carboxylicacid tert-butyl ester obtained in Step D (140 mg) and triethylamine(0.28 ml) in dichloromethane (5 ml) at 0° C. was added2-chloroisonicotinoyl chloride (176 mg). After stirring at roomtemperature for 1 hour, the solution was diluted with dichloromethane,washed with water, dried (sodium sulfate and concentrated in vacuo. Theresidue was disoolved in dichloromethane (12.5 ml) and trifluoroaceticacid (1.25 ml) was added. The reaction mixture was stirred at roomtemperature for 1 hour, diluted with dichloromethane, neutralised withsaturated sodium bicarbonate, dried (sodium sulfate) and concentrated invacuo. The residue was dissolved in acetonitrile (10 ml);diisopropylethylamine (0.13 ml) and 4-chlorocinnamyl chloride (93 mg)were added and the resulting mixture was stirred at room temperature for12 hours then the solvent was evaporated in vacuo. The residue waspurified by silica gel chromatography (eluent cyclohexane:ethyl acetate6:4) to afford the title product (143 mg), which was characterised byits mass and NMR spectra. MS (ES+) 478/480 (M+H⁺).

Compound LXXI-26 was prepared according to procedures analogous to thosedescribed in Example 2.

EXAMPLE 3

This Example illustrates the preparation of compound III-49,5-Chloro-1-(2-chloropyridin-4-yl)carbonyl-1′-[trans-3-(4-chlorophenyl)allyl]spiro[indoline-3,3′-pyrrolidine]

Step A: To a stirred solution of triphenylphosphine (2.75 g) intetrahydrofuran (60 ml) at −10° C. under argon was added dropwisediisopropylazodicarboxylate (DIAD, 2.1 ml); the resulting suspension wasstirred at −10° C. for 15 min then4-chloro-2-iodo-N-methanesulfonyl-aniline (3.1 g) was added as a solidfollowed by 2-methylene-butane-1,4-diol (0.95 g) dissolved in a minimumof tetrahydrofuran. The reaction mixture was stirred at room temperaturefor 6 hours, the solvent was evaporated in vacuo and the residue waspurified by silica gel chromatography (eluent ethyl acetate:cyclohexane4:6) to affordN-(4-Chloro-2-iodo-phenyl)-N-(4-hydroxy-2-methylene-butyl)-methanesulfonamide(3.5 g) contaminated with triphenylphosphine oxide.

Step B: To a stirred solution ofN-(4-Chloro-2-iodo-phenyl)-N-(4-hydroxy-2-methylene-butyl)-methanesulfonamideobtained in Step A and triphenylphosphine (3.5 g) in dimethylacetamide(80 ml) at −10° C. under argon was added carbon tetrabromide (4.5 g).The reaction mixture was stirred at −10° C. for 45 min (a precipitateformed). Sodium azide (2 g) was added in one portion and the reactionmixture was stirred at 45° C. for 1 hour, cooled to room temperature,poured into water, extracted with ethyl acetate; the organic layer waswashed with brine, dried (Na₂SO₄) and concentrated in vacuo. The residuewas purified by silica gel chromatography (eluent cyclohexane:ethylacetate 7:3) to affordN-(4-Chloro-2-iodo-phenyl)-N-(4-azido-2-methylene-butyl)-methanesulfonamide(1.96 g). ¹H NMR (CDCl₃, 400 MHz) 2.50 (m, 2H), 3.48 (m, 2H), 4.19 (d,J=12.0 Hz, 1H), 4.40 (d, J=12.0 Hz, 1H), 4.90 (s, 1H), 5.01 (s, 1H),7.29 (d, J=8.5 Hz, 1H), 7.36 (dd, J=0.9H, 8.5 Hz, 1H), 7.92 (d, J=0.9Hz, 1H).

Step C: A degassed solution ofN-(4-Chloro-2-iodo-phenyl)-N-(4-azido-2-methylene-butyl)-methanesulfonamide(1.38 g) in benzene (200 ml) was heated to reflux under argon.Tris(trimethylsilyl)silane (1.32 ml) was added dropwise followed by1,1′-azobis(cyclohexane carbonitrile) (110 mg). The reaction mixture wasstirred at reflux for 20 hours then concentrated in vacuo. The residuewas dissolved in ethyl acetate (60 ml), extracted with HC12N (3×60 ml).The aqueous layer was basified with 2N sodium hydroxide (250 ml) thenextracted with ethyl acetate (3×150 ml). The combined organic layerswere dried over sodium sulfate and the solvent evaporated in vacuo toafford 1-methanesulfonyl-5-chloro-spiro[indoline-3,3′-pyrrolidine] (766mg) which was used as such for the next step.

Step D: To a solution of1-methanesulfonyl-5-chloro-spiro[indoline-3,3′-pyrrolidine] (725 mg) inacetonitrile (40 ml) were added diisopropylethylamine (0.66 ml) and4-chloro-cinnamyl chloride (467 mg). The resulting solution was stirredat room temperature for 12 hours, diluted with ethyl acetate, washedwith water, brine, dried (Na₂SO₄) and concentrated in vacuo. The residuewas purified by silica gel chromatography (eluent cyclohexane:ethylacetate 6:4) to afford1-methanesulfonyl-5-chloro-1′-[trans-3-(4-chlorophenyl)allyl]spiro[indoline-3,3′-pyrrolidine](500 mg) which was characterised by its mass and NMR spectra. MS (ES+)437/439 (M+H⁺).

Step E: A solution of1-methanesulfonyl-5-chloro-1′-[trans-3-(4-chlorophenyl)allyl]spiro[indoline-3,3′-pyrrolidine]obtained in Step D (256 mg) in toluene (25 ml) under argon was treatedwith sodium bis(2-methoxyethoxy)aluminium hydride (Red-Al, 65% intoluene, 0.67 ml) and the reaction mixture was stirred at 100° C. for 1hour, cooled to room temperature, quenched by addition of ethyl acetate(10 ml), stirred for 15 min and concentrated in vacuo. The residue waspurified by silica gel chromatography (eluent ethyl acetate:methanol95:5) to afford5-chloro-1′-[trans-3-(4-chlorophenyl)allyl]spiro[indoline-3,3′-pyrrolidine](157 mg) as a yellow oil, which was characterised by its mass and NMRspectra.

Step F: A solution of5-chloro-1′-[trans-3-(4-chlorophenyl)allyl]spiro[indoline-3,3′-pyrrolidine](150 mg) and triethylamine (0.24 ml) in dichloromethane (5 ml) at 0° C.under argon was treated with 2-chloro-isonicotinoyl chloride (147 mg).The resulting solution was stirred at room temperature for 1 hour,poured into saturated aqueous sodium bicarbonate, extracted with ethylacetate, dried (Na₂SO₄) and concentrated in vacuo. Silica gelchromatography of the residue (eluent cyclohexane:ethyl acetate 6:4)afforded the title compound,1-(2-chloropyridin-4-yl)carbonyl-1′-[trans-3-(4-chlorophenyl)allyl]spiro[indoline-3,3′-pyrrolidine](95 mg), which was characterised by its mass and NMR spectra. MS (ES+)498/500 (M+H⁺).

Compound III-3 was prepared according to procedures analogous to thosedescribed in Example 3.

EXAMPLE 4

This Example illustrates the pesticidal/insecticidal properties ofcompounds of formula (I). Test against were performed as follows:

Spodoptera littoralis (Egyptian Cotton Leafworm)

Cotton leaf discs were placed on agar in a 24-well microtiter plate andsprayed with test solutions at an application rate of 200 ppm. Afterdrying, the leaf discs were infested with 5 L₁ larvae. The samples werechecked for mortality, repellent effect, feeding behaviour, and growthregulation 3 days after treatment (DAT). The following compounds gave atleast 80% control of Spodoptera littoralis: 111-49 and CXXXIX-49.Heliothis virescens (Tobacco budworm): Eggs (0-24 h old) were placed in24-well microtiter plate on artificial diet and treated with testsolutions at an application rate of 200 ppm by pipetting. After anincubation period of 4 days, samples were checked for egg mortality,larval mortality, and growth regulation. The following compounds gave atleast 80% control of Heliothis virescen: III-3, III-49, CXXXIX-49 andCXLI-49.

Plutella xylostella (Diamond Back Moth):

24-well microtiter plate (MTP) with artificial diet was treated withtest solutions at an application rate of 18.2 ppm by pipetting. Afterdrying, the MTP's were infested with larvae (L2)(10-15 per well). Afteran incubation period of 5 days, samples were checked for larvalmortality, antifeedant and growth regulation. The following compoundsgave at least 80% control of Plutella xylostella: III-49 and CXXXIX-49.

Aedes aegypti (Yellow Fever Mosquito):

10-15 Aedes larvae (L2) together with a nutrition mixture are placed in96-well microtiter plates. Test solutions at an application rate of 2ppm are pipetted into the wells. 2 days later, insects were checked formortality and growth inhibition. The following compounds gave at least80% control of Aedes aegypti: III-49 and CXLI-49.

1. A compound of formula I′

wherein Y is CO, R² and R³ are both hydrogen, R¹ is hydrogen, C₁₋₆alkyl, C₁₋₆ cyanoalkyl, C₁₋₆ haloalkyl, C₃₋₇ cycloalkyl(C₁₋₄)alkyl, C₁₋₆alkoxy(C₁₋₆)alkyl, heteroaryl(C₁₋₆)alkyl (wherein the heteroaryl groupmay be optionally substituted by halo, nitro, cyano, C₁₋₆ alkyl, C₁₋₆haloalkyl, C₁₋₆ alkoxy, C₁₋₆ haloalkoxy, C₁₋₆ alkylsulfonyl, C₁₋₆alkylsulfinyl, C₁₋₆ alkylthio, C₁₋₆ alkoxycarbonyl, C₁₋₆alkylcarbonylamino, arylcarbonyl, or two adjacent positions on theheteroaryl system may be cyclised to form a 5, 6 or 7 memberedcarbocyclic or heterocyclic ring, itself optionally substituted withhalogen), aryl(C₁₋₆)alkyl (wherein the aryl group may be optionallysubstituted by halo, nitro, cyano, C₁₋₆ alkyl, C₁₋₆ haloalkyl, C₁₋₆alkoxy, C₁₋₆ haloalkoxy, C₁₋₆ alkylsulfonyl, C₁₋₆ alkylsulfinyl, C₁₋₆alkylthio, C₁₋₆ alkoxycarbonyl, C₁₋₆ alkylcarbonylamino, arylcarbonyl,or two adjacent positions on the aryl system may be cyclised to form a5, 6 or 7 membered carbocyclic or heterocyclic ring, itself optionallysubstituted with halogen), C₁₋₆ alkylcarbonylamino(C₁₋₆)alkyl, aryl(which may be optionally substituted by halo, nitro, cyano, C₁₋₆ alkyl,C₁₋₆ haloalkyl, C₁₋₆ alkoxy, C₁₋₆ haloalkoxy, C₁₋₆ alkylsulfonyl, C₁₋₆alkylsulfinyl, C₁₋₆ alkylthio, C₁₋₆ alkoxycarbonyl, C₁₋₆alkylcarbonylamino, arylcarbonyl, or two adjacent positions on the arylsystem may be cyclised to form a 5, 6 or 7 membered carbocyclic orheterocyclic ring, itself optionally substituted with halogen),heteroaryl (which may be optionally substituted by halo, nitro, cyano,C₁₋₆ alkyl, C₁₋₆ haloalkyl, C₁₋₆ alkoxy, C₁₋₆ haloalkoxy, C₁₋₆alkylsulfonyl, C₁₋₆ alkylsulfinyl, C₁₋₆ alkylthio, C₁₋₆ alkoxycarbonyl,C₁₋₆ alkylcarbonylamino, arylcarbonyl, or two adjacent positions on theheteroaryl system may be cyclised to form a 5, 6 or 7 memberedcarbocyclic or heterocyclic ring, itself optionally substituted withhalogen), C₁₋₆ alkoxy, C₁₋₆ haloalkoxy, phenoxy (wherein the phenylgroup is optionally substituted by halogen, C₁₋₄ alkyl, C₁₋₄ alkoxy,C₁₋₄ haloalkyl, C₁₋₄ haloalkoxy, CN, NO₂, aryl, heteroaryl, amino ordialkylamino), heteroaryloxy (optionally substituted by halo, nitro,cyano, C₁₋₆ alkyl, C₁₋₆ haloalkyl, C₁₋₆ alkoxy or C₁₋₆ haloalkoxy),heterocyclyloxy (optionally substituted by halo, C₁₋₆ alkyl, C₁₋₆haloalkyl, C₁₋₆ alkoxy or C₁₋₆ haloalkoxy), cyano, C₂₋₆ alkenyl, C₂₋₆alkynyl, C₃₋₆ cycloalkyl, C₅₋₇ cycloalkenyl, heterocyclyl (optionallysubstituted by halo, nitro, cyano, C₁₋₆ alkyl, C₁₋₆ haloalkyl, C₁₋₆alkoxy or C₁₋₆ haloalkoxy), C₁₋₆ alkylthio, C₁₋₆ haloalkylthio orNR¹³R¹⁴ where R¹³ and R¹⁴ are independently hydrogen, C₁₋₆ alkyl, C₁₋₆haloalkyl, C₁₋₆ alkoxy(C₁₋₆)alkyl, phenyl (which may be optionallysubstituted by halogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ haloalkyl, C₁₋₄haloalkoxy, CN, NO₂, aryl, heteroaryl, amino, dialkylamino or C₁₋₄alkoxycarbonyl), phenyl (C₁₋₆)alkyl (wherein the phenyl group may beoptionally substituted by halogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄haloalkyl, C₁₋₄ haloalkoxy, CN, NO₂, aryl, heteroaryl, amino,dialkylamino, C₁₋₆ alkylsulfonyl, C₁₋₆ alkoxycarbonyl, or two adjacentpositions on the phenyl ring may be cyclised to form a 5, 6 or 7membered carbocyclic or heterocyclic ring, itself optionally substitutedwith halogen), heteroaryl (C₁₋₆)alkyl (wherein the heteroaryl group maybe optionally substituted by halo, nitro, cyano, C₁₋₆ alkyl, C₁₋₆haloalkyl, C₁₋₆ alkoxy, C₁₋₆ haloalkoxy, C₁₋₆ alkylsulfonyl, C₁₋₆alkylsulfinyl, C₁₋₆ alkylthio, C₁₋₆ alkoxycarbonyl, C₁₋₆alkylcarbonylamino, arylcarbonyl, or two adjacent positions on theheteroaryl system may be cyclised to form a 5, 6 or 7 memberedcarbocyclic or heterocyclic ring, itself optionally substituted withhalogen) or heteroaryl (which may be optionally substituted by halo,nitro, cyano, C₁₋₆ alkyl, C₁₋₆ haloalkyl, C₁₋₆ alkoxy or C₁₋₆haloalkoxy, C₁₋₄ alkoxycarbonyl C₁₋₆ alkylcarbonylamino,phenyloxycarbonylamino (wherein the phenyl group is optionallysubstituted by halogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ haloalkyl, C₁₋₄haloalkoxy, CN, NO₂, aryl, heteroaryl, amino or dialkylamino), amino,C₁₋₆ alkylamino or phenylamino (wherein the phenyl group is optionallysubstituted halogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ haloalkyl, C₁₋₄haloalkoxy, CN, NO₂, aryl, heteroaryl, amino or dialkylamino)); each R⁴is independently halogen, cyano, C₁₋₈ alkyl, C₁₋₈ haloalkyl, C₁₋₆cyanoalkyl, C₁₋₆ alkoxy(C₁₋₆)alkyl, C₃₋₇ cycloalkyl(C₁₋₆)alkyl, C₅₋₆cycloalkenyl(C₁₋₆)alkyl, C₃₋₆ alkenyloxy(C₁₋₆)alkyl, C₃₋₆alkynyloxy(C₁₋₆)alkyl, aryloxy(C₁₋₆)alkyl, C₁₋₆ carboxyalkyl, C₁₋₆alkylcarbonyl(C₁₋₆)alkyl, C₂₋₆ alkenylcarbonyl(C₁₋₆)alkyl, C₂₋₆alkynylcarbonyl(C₁₋₆)-alkyl, C₁₋₆ alkoxycarbonyl(C₁₋₆)alkyl, C₃₋₆alkenyloxycarbonyl(C₁₋₆)alkyl, C₃₋₆ alkynyloxycarbonyl(C₁₋₆)alkyl,aryloxycarbonyl(C₁₋₆)alkyl, C₁₋₆ alkylthio(C₁₋₆)alkyl, C₁₋₆alkylsulfinyl(C₁₋₆)alkyl, C₁₋₆ alkylsulfonyl(C₁₋₆)alkyl,aminocarbonyl(C₁₋₆)alkyl, C₁₋₆alkylaminocarbonyl(C₁₋₆)alkyl,di(C₁₋₆)alkylaminocarbonyl(C₁₋₆)alkyl, phenyl(C₁₋₄)alkyl (wherein thephenyl group is optionally substituted by halogen, C₁₋₄ alkyl, C₁₋₄alkoxy, C₁₋₄ haloalkyl, C₁₋₄ haloalkoxy, CN, NO₂, aryl, heteroaryl,amino or dialkylamino), heteroaryl(C₁₋₄)alkyl (wherein the heteroarylgroup is optionally substituted by halo, nitro, cyano, C₁₋₆ alkyl, C₁₋₆haloalkyl, C₁₋₆ alkoxy or C₁₋₆ haloalkoxy), heterocyclyl(C₁₋₄)alkyl(wherein the heterocyclyl group is optionally substituted by halo,nitro, cyano, C₁₋₆ alkyl, C₁₋₆ haloalkyl, C₁₋₆ alkoxy or C₁₋₆haloalkoxy), C₂₋₆ alkenyl, aminocarbonyl(C₂₋₆)alkenyl, C₁₋₆alkylaminocarbonyl(C₂₋₆)alkenyl,di(C₁₋₆)alkylaminocarbonyl(C₂₋₆)alkenyl, phenyl(C₂₋₄)-alkenyl, (whereinthe phenyl group is optionally substituted by halogen, C₁₋₄ alkyl, C₁₋₄alkoxy, C₁₋₄ haloalkyl, C₁₋₄ haloalkoxy, CN, NO₂, aryl, heteroaryl,amino or dialkylamino), C₂₋₆ alkynyl, trimethylsilyl(C₂₋₆)alkynyl,aminocarbonyl(C₂₋₆)alkynyl, C₁₋₆ alkylaminocarbonyl(C₂₋₆)alkynyl,di(C₁₋₆)alkylaminocarbonyl(C₂₋₆)alkynyl, C₁₋₆ alkoxycarbonyl, C₃₋₇cycloalkyl, C₃₋₇ halocycloalkyl, C₃₋₇ cyanocycloalkyl,C₁₋₃alkyl(C₃₋₇)-cycloalkyl, C₁₋₃alkyl(C₃₋₇)halocycloalkyl,phenyl(optionally substituted by halogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄haloalkyl, C₁₋₄ haloalkoxy, CN, NO₂, aryl, heteroaryl, amino ordialkylamino), heteroaryl (optionally substituted by halo, nitro, cyano,C₁₋₆ alkyl, C₁₋₆ haloalkyl, C₁₋₆ alkoxy or C₁₋₆ haloalkoxy),heterocyclyl (wherein the heterocyclyl group is optionally substitutedby halo, nitro, cyano, C₁₋₆ alkyl, C₁₋₆ haloalkyl, C₁₋₆ alkoxy or C₁₋₆haloalkoxy), or 2 adjacent groups R⁴ together with the carbon atoms towhich they are attached form a 4, 5, 6 or 7 membered carbocylic orheterocyclic ring which may be optionally substituted by halogen, C₁₋₈alkoxy, C₁₋₆ haloalkoxy, phenoxy (optionally substituted by halo, nitro,cyano, C₁₋₆ alkyl, C₁₋₆ haloalkyl, C₁₋₆ alkoxy or C₁₋₆ haloalkoxy),heteroaryloxy (optionally substituted by halo, nitro, cyano, C₁₋₆ alkyl,C₁₋₆ haloalkyl, C₁₋₆ alkoxy or C₁₋₆ haloalkoxy), C₁₋₈ alkylthio orR¹⁹R²⁰N where R¹⁹ and R²⁰ are, independently, hydrogen, C₁₋₈ alkyl, C₃₋₇cycloalkyl, C₃₋₆ alkenyl, C₃₋₆ alkynyl, C₂₋₆ haloalkyl, C₁₋₆alkoxycarbonyl or R¹⁹ and R²⁰ together with the N atom to which they areattached form a five, six or seven-membered heterocyclic ring which maycontain one or two further heteroatoms selected from O, N or S and whichmay be optionally substituted by one or two C₁₋₆ alkyl groups; n is 0,1, 2 or 3; each Ra is independently hydrogen, halo, cyano, C₁₋₃ alkyl,hydroxy or two Ra groups together with the carbon atom to which they areattached form a carbonyl group; p is 1 or 2 and q is 2 or 3; providedthat when p is 2 then q is not 2; R⁸ is C₁₋₁₀ alkyl, C₁₋₁₀ haloalkyl,aryl(C₁₋₆)alkyl (wherein the aryl group is optionally substituted byhalogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ haloalkyl, C₁₋₄ haloalkoxy, CN,NO₂, aryl, heteroaryl, amino or dialkylamino), heteroaryl(C₁₋₆)alkyl(wherein the heteroaryl group is optionally substituted by halogen, C₁₋₄alkyl, C₁₋₄ alkoxy, C₁₋₄ haloalkyl, C₁₋₄ haloalkoxy, CN, NO₂, aryl,heteroaryl, amino or dialkylamino), arylcarbonyl-(C₁₋₆)alkyl (whereinthe aryl group may be optionally substituted by halogen, C₁₋₄ alkyl,C₁₋₄ alkoxy, C₁₋₄ haloalkyl, C₁₋₄ haloalkoxy, CN, NO₂, aryl, heteroaryl,amino or dialkylamino and the alkyl group may be optionally substitutedby aryl), C₂₋₈ alkenyl, C₂₋₈ haloalkenyl, aryl(C₂₋₆)-alkenyl (whereinthe aryl group is optionally substituted halogen, C₁₋₄ alkyl, C₁₋₄alkoxy, C₁₋₄ haloalkyl, C₁₋₄ haloalkoxy, CN, NO₂, aryl, heteroaryl,amino or dialkylamino, C₁₋₆ alkoxycarbonyl, or two adjacent substituentscan cyclise to form a 5, 6 or 7 membered carbocyclic or heterocyclicring), heteroaryl(C₂₋₆)-alkenyl (wherein the heteroaryl group isoptionally substituted halogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ haloalkyl,C₁₋₄ haloalkoxy, CN, NO₂, aryl, heteroaryl, amino or dialkylamino, C₁₋₆alkoxycarbonyl, or two adjacent substituents can cyclise to form a 5, 6or 7 membered carbocyclic or heterocyclic ring), C₂₋₆ alkynyl,phenyl(C₂₋₆)alkynyl (wherein the phenyl group is optionally substitutedby halogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ haloalkyl, C₁₋₄ haloalkoxy,CN, NO₂, aryl, heteroaryl, amino or dialkylamino), C₃₋₇ cycloalkyl, C₁₋₆alkoxycarbonyl, C₁₋₆ alkylcarbonyl, C₁₋₆ haloalkylcarbonyl oraryl(C₂₋₆)alkenylcarbonyl (wherein the aryl group may be optionallysubstituted halogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ haloalkyl, C₁₋₄haloalkoxy, CN, NO₂, aryl, heteroaryl, amino or dialkylamino), or—C(R⁵¹)(R⁵²)—[CR⁵³═CR⁵⁴]z-R⁵⁵ where z is 1 or 2, R⁵¹ and R⁵² are eachindependently H, halo or C₁₋₂ alkyl, R⁵³ and R⁵⁴ are each independentlyH, halogen, C₁₋₄ alkyl or C₁₋₄ haloalkyl and R⁵⁵ is aryl (wherein thearyl group may be optionally substituted by one or more substituentsindependently selected from halogen, C₁₋₆ alkyl, C₁₋₆ haloalkyl, C₁₋₆alkoxy(C₁₋₆)alkyl, C₁₋₆ alkoxy, C₁₋₆ haloalkoxy, C₁₋₆ alkylthio, C₁₋₆haloalkylthio, C₁₋₆ alkylsulfinyl, C₁₋₆ haloalkylsulfinyl, C₁₋₆alkylsulfonyl, C₁₋₆ haloalkylsulfonyl, C₂₋₆ alkenyl, C₂₋₆ haloalkenyl,C₂₋₆ alkynyl, C₃₋₇ cycloalkyl, nitro, cyano, CO₂H, C₁₋₆ alkylcarbonyl,C₁₋₆ alkoxycarbonyl, aryl, heteroaryl, R²⁵R²⁶N or R²⁷R²⁸NC(O); whereinR²⁵, R²⁶, R²⁷ and R²⁸ are, independently, hydrogen or C₁₋₆ alkyl) orheteroaryl (wherein the heteroaryl group may be optionally substitutedby one or more substituents independently selected from halogen, C₁₋₆alkyl, C₁₋₆ haloalkyl, C₁₋₆ alkoxy(C₁₋₆)alkyl, C₁₋₆ alkoxy, C₁₋₆haloalkoxy, C₁₋₆ alkylthio, C₁₋₆ haloalkylthio, C₁₋₆ alkylsulfinyl, C₁₋₆haloalkylsulfinyl, C₁₋₆ alkylsulfonyl, C₁₋₆ haloalkylsulfonyl, C₂₋₆alkenyl, C₂₋₆ haloalkenyl, C₂₋₆ alkynyl, C₃₋₇ cycloalkyl, nitro, cyano,CO₂H, C₁₋₆ alkylcarbonyl, C₁₋₆ alkoxycarbonyl, aryl, heteroaryl, R²⁵R²⁶Nor R²⁷R²⁸NC(O); wherein R²⁵, R²⁶, R²⁷ and R²⁸ are, independently,hydrogen or C₁₋₆ alkyl); or salts or N-oxides thereof provided that whenn is 0, p is 1, q is 2, R¹ is CH₃ and all groups Ra are H then R⁸ is notH, methyl, benzyl or CH₂—CH═CH₂ and when n is 0, (CRa₂)_(p) isCH-phenyl, (CRa₂)_(q) is (CH₂)₂ and R¹ is methyl then R⁸ is not COOCH₃.2. A compound of formula II

wherein Y, n, p, q, R¹, R², R³, R⁴ and Ra are as defined in claim 1 andR⁸ is hydrogen or tert-butoxycarbonyl.